Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Faricimab (RO6867461) in Participants With Diabetic Macular Edema (YOSEMITE) (NCT NCT03622580)

Last Updated: 2025-07-11

Results Overview

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), baseline BCVA (\<64 vs. ≥64 letters), prior intravitreal anti-VEGF therapy (yes vs. no), and region of enrollment. An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. Invalid BCVA values were excluded. 97.5% CI is a rounding of 97.52% CI.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

940 participants

Primary outcome timeframe

From Baseline through Week 56

Results posted on

2025-07-11

Participant Flow

Participant milestones

Participant milestones
Measure	A: Faricimab 6 mg Q8W Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Overall Study STARTED	315	313	312
Overall Study Received at Least One Dose of Study Drug	313	313	311
Overall Study Completed up to Week 56	291	289	292
Overall Study COMPLETED	263	269	260
Overall Study NOT COMPLETED	52	44	52

Reasons for withdrawal

Reasons for withdrawal
Measure	A: Faricimab 6 mg Q8W Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Overall Study Death	16	21	13
Overall Study Adverse Event	6	6	5
Overall Study Withdrawal by Subject	12	7	19
Overall Study Lost to Follow-up	12	9	9
Overall Study Protocol Violation	1	0	1
Overall Study Physician Decision	3	0	1
Overall Study Pregnancy	0	1	0
Overall Study Lack of Efficacy	0	0	1
Overall Study Other	2	0	3

Baseline Characteristics

The ITT and Treatment-Naive (TN) Populations are grouped according to treatment assigned at randomization. The ITT Population (940) includes all global participants randomized in the study. The TN Population (725), a subset of ITT, includes randomized participants who had not received any IVT anti-VEGF agents in the study eye before randomization.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: From Baseline through Week 56

Population: ITT Population and Treatment-Naive Population

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations ITT Population	11.6 ETDRS Letters Interval 10.3 to 12.9	10.9 ETDRS Letters Interval 9.6 to 12.2	10.7 ETDRS Letters Interval 9.4 to 12.0
Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations Treatment-Naive Population	11.4 ETDRS Letters Interval 9.9 to 12.8	11.3 ETDRS Letters Interval 9.8 to 12.8	10.6 ETDRS Letters Interval 9.1 to 12.1

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: ITT Population and Treatment-Naive Population. Only participants with non-missing, valid assessments at Baseline and Week 52 were included in the analysis.

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 97.5% confidence interval (CI) is a rounding of 97.52% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=242 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=229 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=237 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale at Week 52, ITT and Treatment-Naive Populations ITT Population	42.5 Percentage of participants Interval 35.5 to 49.5	35.8 Percentage of participants Interval 29.1 to 42.5	46.0 Percentage of participants Interval 38.8 to 53.1
Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale at Week 52, ITT and Treatment-Naive Populations Treatment-Naive Population	47.6 Percentage of participants Interval 39.5 to 55.8	42.5 Percentage of participants Interval 34.4 to 50.6	49.7 Percentage of participants Interval 41.2 to 58.2

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 16	10.0 ETDRS Letters Interval 9.2 to 10.8	9.7 ETDRS Letters Interval 8.8 to 10.5	9.1 ETDRS Letters Interval 8.2 to 9.9
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 36	11.7 ETDRS Letters Interval 10.7 to 12.8	10.4 ETDRS Letters Interval 9.4 to 11.4	10.1 ETDRS Letters Interval 9.1 to 11.1
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 68	11.4 ETDRS Letters Interval 10.1 to 12.6	11.3 ETDRS Letters Interval 10.0 to 12.5	10.2 ETDRS Letters Interval 8.9 to 11.5
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 4	6.7 ETDRS Letters Interval 6.0 to 7.4	6.5 ETDRS Letters Interval 5.8 to 7.2	5.5 ETDRS Letters Interval 4.8 to 6.3
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 8	8.2 ETDRS Letters Interval 7.4 to 9.0	8.1 ETDRS Letters Interval 7.3 to 8.8	7.2 ETDRS Letters Interval 6.4 to 7.9
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 12	9.2 ETDRS Letters Interval 8.4 to 10.0	9.1 ETDRS Letters Interval 8.3 to 9.9	8.2 ETDRS Letters Interval 7.4 to 9.0
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 20	9.9 ETDRS Letters Interval 9.0 to 10.8	9.8 ETDRS Letters Interval 8.9 to 10.7	9.6 ETDRS Letters Interval 8.7 to 10.5
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 24	11.3 ETDRS Letters Interval 10.4 to 12.2	9.4 ETDRS Letters Interval 8.5 to 10.3	10.2 ETDRS Letters Interval 9.3 to 11.1
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 28	11.0 ETDRS Letters Interval 10.0 to 11.9	10.5 ETDRS Letters Interval 9.6 to 11.5	9.5 ETDRS Letters Interval 8.6 to 10.5
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 32	10.9 ETDRS Letters Interval 9.9 to 11.9	10.2 ETDRS Letters Interval 9.2 to 11.2	10.2 ETDRS Letters Interval 9.2 to 11.2
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 40	11.4 ETDRS Letters Interval 10.3 to 12.5	10.3 ETDRS Letters Interval 9.2 to 11.4	10.2 ETDRS Letters Interval 9.1 to 11.2
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 44	11.4 ETDRS Letters Interval 10.3 to 12.5	10.7 ETDRS Letters Interval 9.6 to 11.9	9.9 ETDRS Letters Interval 8.8 to 11.0
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 48	11.4 ETDRS Letters Interval 10.3 to 12.5	10.8 ETDRS Letters Interval 9.7 to 11.9	10.5 ETDRS Letters Interval 9.4 to 11.6
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 52	11.0 ETDRS Letters Interval 9.8 to 12.2	10.9 ETDRS Letters Interval 9.7 to 12.2	9.9 ETDRS Letters Interval 8.7 to 11.1
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 56	11.6 ETDRS Letters Interval 10.4 to 12.8	10.6 ETDRS Letters Interval 9.4 to 11.8	10.8 ETDRS Letters Interval 9.7 to 12.0
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 60	12.0 ETDRS Letters Interval 10.8 to 13.1	11.3 ETDRS Letters Interval 10.1 to 12.5	10.3 ETDRS Letters Interval 9.1 to 11.5
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 64	11.5 ETDRS Letters Interval 10.3 to 12.7	10.8 ETDRS Letters Interval 9.6 to 12.0	10.7 ETDRS Letters Interval 9.5 to 12.0
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 72	11.3 ETDRS Letters Interval 10.0 to 12.6	10.7 ETDRS Letters Interval 9.4 to 12.0	10.4 ETDRS Letters Interval 9.1 to 11.7
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 76	11.5 ETDRS Letters Interval 10.1 to 12.9	11.0 ETDRS Letters Interval 9.6 to 12.4	10.2 ETDRS Letters Interval 8.8 to 11.6
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 80	11.1 ETDRS Letters Interval 9.8 to 12.4	10.9 ETDRS Letters Interval 9.6 to 12.2	10.9 ETDRS Letters Interval 9.5 to 12.2
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 84	11.5 ETDRS Letters Interval 10.2 to 12.8	11.8 ETDRS Letters Interval 10.5 to 13.1	9.9 ETDRS Letters Interval 8.6 to 11.2
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 88	10.9 ETDRS Letters Interval 9.5 to 12.3	11.0 ETDRS Letters Interval 9.6 to 12.4	9.8 ETDRS Letters Interval 8.4 to 11.2
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 92	11.2 ETDRS Letters Interval 9.9 to 12.6	11.5 ETDRS Letters Interval 10.1 to 12.9	10.5 ETDRS Letters Interval 9.1 to 11.9
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 96	10.6 ETDRS Letters Interval 9.2 to 12.0	11.1 ETDRS Letters Interval 9.7 to 12.5	11.1 ETDRS Letters Interval 9.7 to 12.6
Change From Baseline in BCVA in the Study Eye Over Time, ITT Population Week 100	10.4 ETDRS Letters Interval 9.0 to 11.8	11.6 ETDRS Letters Interval 10.1 to 13.1	10.5 ETDRS Letters Interval 9.1 to 12.0

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Best-Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline BCVA (continuous), baseline BCVA (\<64 vs. ≥64 letters), and region of enrollment. An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 4	6.8 ETDRS Letters Interval 6.0 to 7.6	6.9 ETDRS Letters Interval 6.1 to 7.7	5.8 ETDRS Letters Interval 5.0 to 6.7
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 48	11.0 ETDRS Letters Interval 9.7 to 12.4	11.2 ETDRS Letters Interval 9.8 to 12.5	10.3 ETDRS Letters Interval 9.0 to 11.7
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 56	11.5 ETDRS Letters Interval 10.1 to 12.8	11.0 ETDRS Letters Interval 9.6 to 12.4	10.9 ETDRS Letters Interval 9.5 to 12.3
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 60	12.0 ETDRS Letters Interval 10.6 to 13.4	11.6 ETDRS Letters Interval 10.2 to 13.0	10.1 ETDRS Letters Interval 8.7 to 11.6
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 84	11.6 ETDRS Letters Interval 10.0 to 13.1	11.9 ETDRS Letters Interval 10.3 to 13.4	9.6 ETDRS Letters Interval 8.0 to 11.1
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 96	10.5 ETDRS Letters Interval 8.9 to 12.1	11.4 ETDRS Letters Interval 9.7 to 13.0	11.1 ETDRS Letters Interval 9.4 to 12.8
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 100	10.5 ETDRS Letters Interval 8.8 to 12.1	11.7 ETDRS Letters Interval 10.0 to 13.4	10.5 ETDRS Letters Interval 8.8 to 12.3
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 8	8.3 ETDRS Letters Interval 7.4 to 9.2	8.7 ETDRS Letters Interval 7.8 to 9.5	7.2 ETDRS Letters Interval 6.3 to 8.1
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 12	9.3 ETDRS Letters Interval 8.4 to 10.2	9.6 ETDRS Letters Interval 8.7 to 10.5	8.5 ETDRS Letters Interval 7.6 to 9.4
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 16	10.0 ETDRS Letters Interval 9.1 to 10.9	10.1 ETDRS Letters Interval 9.2 to 11.1	9.3 ETDRS Letters Interval 8.4 to 10.3
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 20	9.7 ETDRS Letters Interval 8.6 to 10.7	10.3 ETDRS Letters Interval 9.3 to 11.4	9.7 ETDRS Letters Interval 8.7 to 10.8
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 24	11.2 ETDRS Letters Interval 10.2 to 12.2	9.8 ETDRS Letters Interval 8.7 to 10.8	10.5 ETDRS Letters Interval 9.4 to 11.5
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 28	11.0 ETDRS Letters Interval 9.9 to 12.1	11.0 ETDRS Letters Interval 9.9 to 12.1	9.6 ETDRS Letters Interval 8.5 to 10.7
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 32	10.9 ETDRS Letters Interval 9.8 to 12.1	10.6 ETDRS Letters Interval 9.5 to 11.8	10.3 ETDRS Letters Interval 9.1 to 11.5
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 36	11.9 ETDRS Letters Interval 10.7 to 13.1	10.6 ETDRS Letters Interval 9.4 to 11.8	10.3 ETDRS Letters Interval 9.1 to 11.6
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 40	11.4 ETDRS Letters Interval 10.1 to 12.7	10.7 ETDRS Letters Interval 9.4 to 12.1	10.0 ETDRS Letters Interval 8.7 to 11.3
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 44	11.4 ETDRS Letters Interval 10.1 to 12.7	11.3 ETDRS Letters Interval 10.0 to 12.6	10.1 ETDRS Letters Interval 8.8 to 11.4
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 52	10.7 ETDRS Letters Interval 9.3 to 12.2	11.3 ETDRS Letters Interval 9.9 to 12.8	9.6 ETDRS Letters Interval 8.2 to 11.1
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 64	11.5 ETDRS Letters Interval 10.0 to 13.0	11.0 ETDRS Letters Interval 9.5 to 12.4	10.6 ETDRS Letters Interval 9.1 to 12.1
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 68	11.3 ETDRS Letters Interval 9.8 to 12.8	11.4 ETDRS Letters Interval 9.9 to 12.9	10.3 ETDRS Letters Interval 8.8 to 11.8
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 72	11.3 ETDRS Letters Interval 9.8 to 12.8	10.8 ETDRS Letters Interval 9.3 to 12.4	10.2 ETDRS Letters Interval 8.6 to 11.7
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 76	11.4 ETDRS Letters Interval 9.7 to 13.0	10.8 ETDRS Letters Interval 9.2 to 12.5	9.9 ETDRS Letters Interval 8.2 to 11.6
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 80	11.0 ETDRS Letters Interval 9.4 to 12.6	11.1 ETDRS Letters Interval 9.6 to 12.7	10.6 ETDRS Letters Interval 9.0 to 12.2
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 88	10.8 ETDRS Letters Interval 9.1 to 12.5	10.9 ETDRS Letters Interval 9.2 to 12.6	9.4 ETDRS Letters Interval 7.7 to 11.1
Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population Week 92	11.2 ETDRS Letters Interval 9.5 to 12.8	11.6 ETDRS Letters Interval 10.0 to 13.3	10.1 ETDRS Letters Interval 8.4 to 11.7

SECONDARY outcome

Timeframe: Baseline, average of Weeks 48, 52, and 56

Population: ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Only participants with at least one non-missing, valid assessment at Weeks 48, 52, or 56 were included in the analysis.

BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=276 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=276 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=271 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population Gaining ≥10 Letters	58.3 Percentage of participants Interval 52.6 to 64.0	57.6 Percentage of participants Interval 51.8 to 63.4	57.2 Percentage of participants Interval 51.3 to 63.1
Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population Gaining ≥15 Letters	35.5 Percentage of participants Interval 30.1 to 40.9	31.8 Percentage of participants Interval 26.6 to 37.0	29.2 Percentage of participants Interval 23.9 to 34.5
Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population Gaining ≥5 Letters	79.6 Percentage of participants Interval 74.9 to 84.3	81.4 Percentage of participants Interval 76.9 to 86.0	78.9 Percentage of participants Interval 74.1 to 83.8
Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population Gaining ≥0 Letters	94.5 Percentage of participants Interval 91.8 to 97.2	91.4 Percentage of participants Interval 88.1 to 94.6	91.5 Percentage of participants Interval 88.1 to 94.8

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. At each timepoint, only participants with non-missing, valid assessments were included in the analysis.

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 4	13.0 Percentage of participants Interval 9.4 to 16.6	11.4 Percentage of participants Interval 8.0 to 14.9	7.7 Percentage of participants Interval 4.8 to 10.7
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 8	18.8 Percentage of participants Interval 14.8 to 22.9	16.7 Percentage of participants Interval 12.7 to 20.7	13.4 Percentage of participants Interval 9.6 to 17.1
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 12	23.1 Percentage of participants Interval 18.6 to 27.5	22.1 Percentage of participants Interval 17.6 to 26.5	14.9 Percentage of participants Interval 11.0 to 18.9
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 16	27.8 Percentage of participants Interval 22.9 to 32.7	22.2 Percentage of participants Interval 17.7 to 26.8	20.4 Percentage of participants Interval 15.9 to 24.9
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 20	28.4 Percentage of participants Interval 23.4 to 33.4	24.0 Percentage of participants Interval 19.4 to 28.6	25.6 Percentage of participants Interval 20.8 to 30.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 24	34.2 Percentage of participants Interval 29.0 to 39.3	25.7 Percentage of participants Interval 21.0 to 30.5	26.8 Percentage of participants Interval 21.8 to 31.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 28	31.2 Percentage of participants Interval 26.2 to 36.3	29.2 Percentage of participants Interval 24.3 to 34.2	23.5 Percentage of participants Interval 18.6 to 28.4
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 32	36.2 Percentage of participants Interval 30.7 to 41.7	25.8 Percentage of participants Interval 21.0 to 30.7	28.5 Percentage of participants Interval 23.1 to 33.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 36	40.2 Percentage of participants Interval 34.6 to 45.8	32.5 Percentage of participants Interval 27.1 to 37.9	24.4 Percentage of participants Interval 19.3 to 29.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 40	37.1 Percentage of participants Interval 31.6 to 42.7	30.3 Percentage of participants Interval 24.9 to 35.6	29.7 Percentage of participants Interval 24.3 to 35.1
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 44	37.1 Percentage of participants Interval 31.7 to 42.6	34.9 Percentage of participants Interval 29.4 to 40.4	29.2 Percentage of participants Interval 23.8 to 34.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 48	39.6 Percentage of participants Interval 33.9 to 45.3	34.0 Percentage of participants Interval 28.7 to 39.3	31.7 Percentage of participants Interval 26.1 to 37.2
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 52	37.2 Percentage of participants Interval 31.7 to 42.7	36.0 Percentage of participants Interval 30.3 to 41.6	31.2 Percentage of participants Interval 25.7 to 36.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 56	38.4 Percentage of participants Interval 32.7 to 44.0	31.5 Percentage of participants Interval 26.1 to 36.9	38.1 Percentage of participants Interval 32.3 to 43.9
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 60	41.3 Percentage of participants Interval 35.5 to 47.1	35.9 Percentage of participants Interval 30.3 to 41.4	34.4 Percentage of participants Interval 28.8 to 40.0
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 64	41.4 Percentage of participants Interval 35.8 to 47.1	34.8 Percentage of participants Interval 29.1 to 40.5	37.5 Percentage of participants Interval 31.7 to 43.4
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 68	43.7 Percentage of participants Interval 37.9 to 49.6	37.1 Percentage of participants Interval 31.4 to 42.8	37.1 Percentage of participants Interval 31.4 to 42.9
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 72	38.2 Percentage of participants Interval 32.6 to 43.8	35.2 Percentage of participants Interval 29.5 to 41.0	34.8 Percentage of participants Interval 29.1 to 40.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 76	44.1 Percentage of participants Interval 38.4 to 49.9	37.2 Percentage of participants Interval 31.3 to 43.1	36.6 Percentage of participants Interval 30.7 to 42.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 80	42.1 Percentage of participants Interval 36.5 to 47.8	36.9 Percentage of participants Interval 31.1 to 42.6	39.3 Percentage of participants Interval 33.4 to 45.3
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 84	41.5 Percentage of participants Interval 35.8 to 47.2	38.8 Percentage of participants Interval 32.9 to 44.6	40.6 Percentage of participants Interval 34.5 to 46.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 88	39.8 Percentage of participants Interval 34.2 to 45.4	35.9 Percentage of participants Interval 30.1 to 41.6	39.2 Percentage of participants Interval 33.2 to 45.2
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 92	41.0 Percentage of participants Interval 35.3 to 46.6	38.8 Percentage of participants Interval 33.0 to 44.7	39.7 Percentage of participants Interval 33.8 to 45.7
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 96	40.2 Percentage of participants Interval 34.5 to 45.8	38.8 Percentage of participants Interval 32.9 to 44.7	41.3 Percentage of participants Interval 35.1 to 47.4
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 100	40.3 Percentage of participants Interval 34.7 to 46.0	40.9 Percentage of participants Interval 34.9 to 46.9	40.2 Percentage of participants Interval 34.2 to 46.1

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 4	31.1 Percentage of participants Interval 26.2 to 36.1	27.1 Percentage of participants Interval 22.2 to 32.0	23.9 Percentage of participants Interval 19.2 to 28.6
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 8	37.1 Percentage of participants Interval 31.8 to 42.3	41.0 Percentage of participants Interval 35.6 to 46.4	30.8 Percentage of participants Interval 25.7 to 35.9
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 12	47.5 Percentage of participants Interval 42.0 to 53.0	46.2 Percentage of participants Interval 40.7 to 51.7	35.5 Percentage of participants Interval 30.2 to 40.8
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 16	48.4 Percentage of participants Interval 42.8 to 54.0	49.7 Percentage of participants Interval 44.1 to 55.3	43.7 Percentage of participants Interval 38.0 to 49.3
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 20	53.1 Percentage of participants Interval 47.6 to 58.6	50.3 Percentage of participants Interval 44.7 to 56.0	45.6 Percentage of participants Interval 40.0 to 51.3
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 24	58.6 Percentage of participants Interval 53.2 to 64.1	48.2 Percentage of participants Interval 42.6 to 53.9	55.6 Percentage of participants Interval 50.0 to 61.2
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 28	57.0 Percentage of participants Interval 51.4 to 62.6	57.2 Percentage of participants Interval 51.6 to 62.9	55.6 Percentage of participants Interval 49.9 to 61.3
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 32	58.5 Percentage of participants Interval 52.8 to 64.2	53.1 Percentage of participants Interval 47.3 to 58.8	56.7 Percentage of participants Interval 50.9 to 62.6
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 36	65.5 Percentage of participants Interval 60.0 to 71.1	55.7 Percentage of participants Interval 49.9 to 61.6	55.6 Percentage of participants Interval 49.7 to 61.5
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 40	60.0 Percentage of participants Interval 54.2 to 65.8	53.2 Percentage of participants Interval 47.2 to 59.2	55.7 Percentage of participants Interval 49.8 to 61.5
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 44	60.5 Percentage of participants Interval 54.7 to 66.2	57.2 Percentage of participants Interval 51.3 to 63.2	55.1 Percentage of participants Interval 49.3 to 61.0
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 48	60.2 Percentage of participants Interval 54.5 to 65.9	61.7 Percentage of participants Interval 55.9 to 67.4	57.0 Percentage of participants Interval 51.0 to 62.9
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 52	59.5 Percentage of participants Interval 53.8 to 65.2	60.2 Percentage of participants Interval 54.3 to 66.2	59.9 Percentage of participants Interval 54.0 to 65.8
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 56	62.6 Percentage of participants Interval 56.9 to 68.3	59.0 Percentage of participants Interval 53.0 to 64.9	63.5 Percentage of participants Interval 57.7 to 69.4
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 60	62.6 Percentage of participants Interval 56.9 to 68.3	60.7 Percentage of participants Interval 54.9 to 66.5	59.4 Percentage of participants Interval 53.5 to 65.2
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 64	60.0 Percentage of participants Interval 54.3 to 65.7	59.6 Percentage of participants Interval 53.8 to 65.5	64.9 Percentage of participants Interval 59.2 to 70.7
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 68	58.9 Percentage of participants Interval 53.1 to 64.7	59.4 Percentage of participants Interval 53.5 to 65.4	60.1 Percentage of participants Interval 54.2 to 66.0
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 72	61.0 Percentage of participants Interval 55.2 to 66.8	56.8 Percentage of participants Interval 50.7 to 62.9	61.2 Percentage of participants Interval 55.2 to 67.1
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 76	67.8 Percentage of participants Interval 62.3 to 73.3	64.2 Percentage of participants Interval 58.3 to 70.0	60.1 Percentage of participants Interval 54.1 to 66.2
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 80	61.7 Percentage of participants Interval 56.1 to 67.4	60.5 Percentage of participants Interval 54.5 to 66.4	64.0 Percentage of participants Interval 58.1 to 70.0
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 84	64.4 Percentage of participants Interval 58.8 to 70.1	64.4 Percentage of participants Interval 58.6 to 70.2	61.0 Percentage of participants Interval 55.0 to 67.0
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 88	59.8 Percentage of participants Interval 54.0 to 65.7	62.7 Percentage of participants Interval 56.9 to 68.5	59.6 Percentage of participants Interval 53.5 to 65.7
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 92	63.3 Percentage of participants Interval 57.6 to 69.0	64.6 Percentage of participants Interval 58.7 to 70.4	63.2 Percentage of participants Interval 57.3 to 69.1
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 96	59.7 Percentage of participants Interval 53.9 to 65.5	62.5 Percentage of participants Interval 56.5 to 68.6	60.3 Percentage of participants Interval 54.1 to 66.4
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 100	60.5 Percentage of participants Interval 54.8 to 66.2	66.0 Percentage of participants Interval 60.1 to 71.8	63.0 Percentage of participants Interval 57.3 to 68.8

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 44	81.9 Percentage of participants Interval 77.3 to 86.4	77.9 Percentage of participants Interval 73.0 to 82.7	80.7 Percentage of participants Interval 75.9 to 85.4
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 4	62.6 Percentage of participants Interval 57.3 to 67.9	61.1 Percentage of participants Interval 55.7 to 66.5	53.6 Percentage of participants Interval 48.1 to 59.1
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 8	71.1 Percentage of participants Interval 66.1 to 76.0	67.6 Percentage of participants Interval 62.4 to 72.8	64.7 Percentage of participants Interval 59.4 to 70.0
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 12	74.3 Percentage of participants Interval 69.4 to 79.2	75.4 Percentage of participants Interval 70.6 to 80.3	71.9 Percentage of participants Interval 66.9 to 76.9
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 16	81.4 Percentage of participants Interval 77.0 to 85.8	77.5 Percentage of participants Interval 72.7 to 82.2	74.9 Percentage of participants Interval 70.0 to 79.9
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 20	78.4 Percentage of participants Interval 73.7 to 83.1	76.4 Percentage of participants Interval 71.6 to 81.1	78.2 Percentage of participants Interval 73.6 to 82.9
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 24	83.3 Percentage of participants Interval 79.0 to 87.5	71.0 Percentage of participants Interval 65.8 to 76.1	80.5 Percentage of participants Interval 76.0 to 85.0
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 28	81.0 Percentage of participants Interval 76.6 to 85.5	79.1 Percentage of participants Interval 74.4 to 83.8	77.4 Percentage of participants Interval 72.5 to 82.2
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 32	77.1 Percentage of participants Interval 72.2 to 82.0	81.3 Percentage of participants Interval 76.8 to 85.8	79.4 Percentage of participants Interval 74.6 to 84.3
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 36	82.6 Percentage of participants Interval 78.2 to 87.1	78.3 Percentage of participants Interval 73.5 to 83.1	79.2 Percentage of participants Interval 74.4 to 84.1
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 40	84.3 Percentage of participants Interval 80.0 to 88.6	77.1 Percentage of participants Interval 72.0 to 82.2	76.3 Percentage of participants Interval 71.3 to 81.3
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 48	82.0 Percentage of participants Interval 77.5 to 86.6	79.3 Percentage of participants Interval 74.4 to 84.1	79.2 Percentage of participants Interval 74.4 to 84.1
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 52	78.4 Percentage of participants Interval 73.5 to 83.2	81.2 Percentage of participants Interval 76.4 to 85.9	78.4 Percentage of participants Interval 73.5 to 83.4
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 56	81.3 Percentage of participants Interval 76.6 to 86.0	81.4 Percentage of participants Interval 76.7 to 86.1	83.0 Percentage of participants Interval 78.5 to 87.6
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 60	81.3 Percentage of participants Interval 76.7 to 85.9	81.4 Percentage of participants Interval 76.8 to 86.1	80.4 Percentage of participants Interval 75.7 to 85.1
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 64	80.6 Percentage of participants Interval 75.9 to 85.2	79.7 Percentage of participants Interval 74.9 to 84.5	80.2 Percentage of participants Interval 75.4 to 85.1
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 68	78.9 Percentage of participants Interval 74.0 to 83.8	79.1 Percentage of participants Interval 74.2 to 84.0	79.1 Percentage of participants Interval 74.1 to 84.0
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 72	78.1 Percentage of participants Interval 73.2 to 83.0	80.9 Percentage of participants Interval 76.1 to 85.7	79.7 Percentage of participants Interval 74.8 to 84.6
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 76	78.9 Percentage of participants Interval 74.0 to 83.8	82.9 Percentage of participants Interval 78.3 to 87.5	79.9 Percentage of participants Interval 74.9 to 84.8
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 80	80.3 Percentage of participants Interval 75.5 to 85.0	78.3 Percentage of participants Interval 73.2 to 83.4	81.0 Percentage of participants Interval 76.1 to 85.9
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 84	82.0 Percentage of participants Interval 77.5 to 86.5	82.6 Percentage of participants Interval 77.9 to 87.2	77.1 Percentage of participants Interval 71.9 to 82.3
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 88	80.5 Percentage of participants Interval 75.8 to 85.2	80.5 Percentage of participants Interval 75.6 to 85.5	79.3 Percentage of participants Interval 74.2 to 84.3
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 92	82.1 Percentage of participants Interval 77.5 to 86.7	83.2 Percentage of participants Interval 78.6 to 87.7	81.4 Percentage of participants Interval 76.6 to 86.3
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 96	77.4 Percentage of participants Interval 72.5 to 82.4	81.2 Percentage of participants Interval 76.3 to 86.0	82.6 Percentage of participants Interval 77.8 to 87.3
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 100	77.0 Percentage of participants Interval 71.9 to 82.0	85.2 Percentage of participants Interval 80.9 to 89.6	81.1 Percentage of participants Interval 76.3 to 85.9

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 8	91.9 Percentage of participants Interval 88.8 to 94.9	91.1 Percentage of participants Interval 87.9 to 94.2	89.7 Percentage of participants Interval 86.4 to 93.0
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 28	94.1 Percentage of participants Interval 91.4 to 96.8	91.5 Percentage of participants Interval 88.3 to 94.6	90.4 Percentage of participants Interval 87.0 to 93.8
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 44	94.5 Percentage of participants Interval 91.8 to 97.2	91.0 Percentage of participants Interval 87.6 to 94.4	91.0 Percentage of participants Interval 87.6 to 94.4
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 48	93.7 Percentage of participants Interval 90.8 to 96.5	91.3 Percentage of participants Interval 88.0 to 94.6	95.2 Percentage of participants Interval 92.6 to 97.7
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 4	90.8 Percentage of participants Interval 87.7 to 94.0	88.9 Percentage of participants Interval 85.4 to 92.3	86.1 Percentage of participants Interval 82.3 to 90.0
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 12	94.7 Percentage of participants Interval 92.2 to 97.2	92.7 Percentage of participants Interval 89.8 to 95.6	92.5 Percentage of participants Interval 89.6 to 95.4
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 16	94.9 Percentage of participants Interval 92.4 to 97.4	93.7 Percentage of participants Interval 90.9 to 96.4	91.2 Percentage of participants Interval 88.0 to 94.4
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 20	93.1 Percentage of participants Interval 90.2 to 96.0	92.2 Percentage of participants Interval 89.2 to 95.2	93.9 Percentage of participants Interval 91.2 to 96.6
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 24	93.8 Percentage of participants Interval 91.0 to 96.5	89.9 Percentage of participants Interval 86.5 to 93.3	93.1 Percentage of participants Interval 90.2 to 96.0
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 32	95.1 Percentage of participants Interval 92.6 to 97.7	91.3 Percentage of participants Interval 88.0 to 94.6	92.1 Percentage of participants Interval 88.9 to 95.3
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 36	93.2 Percentage of participants Interval 90.2 to 96.2	90.4 Percentage of participants Interval 87.0 to 93.9	92.1 Percentage of participants Interval 88.9 to 95.3
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 40	94.0 Percentage of participants Interval 91.1 to 96.8	93.2 Percentage of participants Interval 90.2 to 96.2	90.9 Percentage of participants Interval 87.5 to 94.3
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 52	91.3 Percentage of participants Interval 88.0 to 94.7	91.0 Percentage of participants Interval 87.5 to 94.5	89.8 Percentage of participants Interval 86.1 to 93.4
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 56	93.9 Percentage of participants Interval 91.0 to 96.7	90.6 Percentage of participants Interval 87.1 to 94.2	91.4 Percentage of participants Interval 88.0 to 94.8
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 60	93.5 Percentage of participants Interval 90.5 to 96.4	92.8 Percentage of participants Interval 89.7 to 95.9	89.5 Percentage of participants Interval 85.9 to 93.2
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 64	92.7 Percentage of participants Interval 89.6 to 95.8	92.0 Percentage of participants Interval 88.7 to 95.2	91.3 Percentage of participants Interval 87.9 to 94.7
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 68	92.9 Percentage of participants Interval 89.8 to 96.0	91.9 Percentage of participants Interval 88.6 to 95.2	92.1 Percentage of participants Interval 88.8 to 95.4
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 72	91.9 Percentage of participants Interval 88.7 to 95.2	90.0 Percentage of participants Interval 86.3 to 93.7	88.5 Percentage of participants Interval 84.6 to 92.5
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 76	91.2 Percentage of participants Interval 87.8 to 94.7	92.5 Percentage of participants Interval 89.4 to 95.7	87.8 Percentage of participants Interval 83.8 to 91.9
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 80	91.5 Percentage of participants Interval 88.1 to 94.9	89.6 Percentage of participants Interval 85.9 to 93.4	89.2 Percentage of participants Interval 85.4 to 93.0
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 84	92.4 Percentage of participants Interval 89.2 to 95.6	93.5 Percentage of participants Interval 90.5 to 96.5	87.1 Percentage of participants Interval 82.9 to 91.2
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 88	90.3 Percentage of participants Interval 86.7 to 93.8	89.9 Percentage of participants Interval 86.1 to 93.7	87.3 Percentage of participants Interval 83.2 to 91.4
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 92	91.1 Percentage of participants Interval 87.6 to 94.6	90.8 Percentage of participants Interval 87.3 to 94.3	89.4 Percentage of participants Interval 85.5 to 93.2
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 96	88.9 Percentage of participants Interval 85.1 to 92.6	90.5 Percentage of participants Interval 86.8 to 94.2	90.7 Percentage of participants Interval 87.0 to 94.4
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 100	86.8 Percentage of participants Interval 82.7 to 90.9	92.0 Percentage of participants Interval 88.7 to 95.4	88.3 Percentage of participants Interval 84.3 to 92.3

SECONDARY outcome

Timeframe: Baseline, average of Weeks 48, 52, and 56

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. Only participants with at least one non-missing, valid assessment at Weeks 48, 52, or 56 were included in the analysis.

BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=215 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=212 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=200 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population Gaining ≥15 Letters	35.5 Percentage of participants Interval 29.3 to 41.7	33.8 Percentage of participants Interval 27.7 to 39.9	28.6 Percentage of participants Interval 22.3 to 34.8
Percentage of Participants Gaining ≥15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population Gaining ≥10 Letters	59.6 Percentage of participants Interval 53.2 to 65.9	57.5 Percentage of participants Interval 50.9 to 64.1	57.5 Percentage of participants Interval 50.7 to 64.4
Percentage of Participants Gaining ≥15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population Gaining ≥5 Letters	77.2 Percentage of participants Interval 71.6 to 82.8	84.5 Percentage of participants Interval 79.6 to 89.3	80.0 Percentage of participants Interval 74.4 to 85.5
Percentage of Participants Gaining ≥15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population Gaining ≥0 Letters	93.5 Percentage of participants Interval 90.2 to 96.8	91.6 Percentage of participants Interval 87.9 to 95.3	91.5 Percentage of participants Interval 87.6 to 95.3

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. At each timepoint, only participants with non-missing, valid assessments were included in the analysis.

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 100	42.5 Percentage of participants Interval 36.1 to 48.9	41.2 Percentage of participants Interval 34.3 to 48.1	41.7 Percentage of participants Interval 34.6 to 48.7
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 16	28.2 Percentage of participants Interval 22.6 to 33.8	24.0 Percentage of participants Interval 18.6 to 29.3	21.3 Percentage of participants Interval 16.0 to 26.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 24	34.3 Percentage of participants Interval 28.4 to 40.2	27.5 Percentage of participants Interval 22.0 to 33.1	27.1 Percentage of participants Interval 21.3 to 32.9
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 28	30.7 Percentage of participants Interval 25.0 to 36.4	32.8 Percentage of participants Interval 26.8 to 38.7	21.5 Percentage of participants Interval 16.0 to 27.0
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 32	37.5 Percentage of participants Interval 31.2 to 43.8	29.5 Percentage of participants Interval 23.6 to 35.4	27.2 Percentage of participants Interval 21.0 to 33.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 36	41.9 Percentage of participants Interval 35.5 to 48.2	34.9 Percentage of participants Interval 28.6 to 41.2	23.5 Percentage of participants Interval 17.6 to 29.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 48	39.6 Percentage of participants Interval 33.1 to 46.0	36.3 Percentage of participants Interval 30.1 to 42.5	32.5 Percentage of participants Interval 26.0 to 39.1
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 56	38.8 Percentage of participants Interval 32.3 to 45.2	34.3 Percentage of participants Interval 27.9 to 40.8	37.7 Percentage of participants Interval 31.0 to 44.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 64	43.5 Percentage of participants Interval 37.0 to 50.0	36.0 Percentage of participants Interval 29.5 to 42.6	37.9 Percentage of participants Interval 31.1 to 44.7
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 68	45.4 Percentage of participants Interval 38.7 to 52.1	39.0 Percentage of participants Interval 32.4 to 45.5	37.4 Percentage of participants Interval 30.7 to 44.2
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 72	39.6 Percentage of participants Interval 33.1 to 46.0	36.6 Percentage of participants Interval 29.8 to 43.3	35.6 Percentage of participants Interval 28.8 to 42.4
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 80	43.2 Percentage of participants Interval 36.8 to 49.7	40.5 Percentage of participants Interval 33.6 to 47.3	39.7 Percentage of participants Interval 32.7 to 46.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 96	41.2 Percentage of participants Interval 34.9 to 47.6	40.1 Percentage of participants Interval 33.2 to 47.0	42.9 Percentage of participants Interval 35.6 to 50.2
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 40	37.7 Percentage of participants Interval 31.2 to 44.1	33.5 Percentage of participants Interval 27.0 to 39.9	27.6 Percentage of participants Interval 21.5 to 33.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 44	39.7 Percentage of participants Interval 33.3 to 46.0	37.0 Percentage of participants Interval 30.6 to 43.4	27.2 Percentage of participants Interval 21.1 to 33.4
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 52	35.9 Percentage of participants Interval 29.6 to 42.1	37.4 Percentage of participants Interval 30.9 to 43.9	30.7 Percentage of participants Interval 24.3 to 37.1
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 60	42.2 Percentage of participants Interval 35.6 to 48.9	38.9 Percentage of participants Interval 32.4 to 45.5	33.1 Percentage of participants Interval 26.6 to 39.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 76	45.3 Percentage of participants Interval 38.8 to 51.8	37.2 Percentage of participants Interval 30.5 to 43.9	37.6 Percentage of participants Interval 30.6 to 44.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 84	43.2 Percentage of participants Interval 36.8 to 49.7	41.2 Percentage of participants Interval 34.3 to 48.1	40.7 Percentage of participants Interval 33.7 to 47.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 88	40.7 Percentage of participants Interval 34.4 to 47.1	38.0 Percentage of participants Interval 31.2 to 44.8	39.1 Percentage of participants Interval 32.1 to 46.2
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 92	42.1 Percentage of participants Interval 35.7 to 48.5	40.4 Percentage of participants Interval 33.6 to 47.3	40.2 Percentage of participants Interval 33.2 to 47.3
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 4	14.9 Percentage of participants Interval 10.6 to 19.3	12.7 Percentage of participants Interval 8.6 to 16.9	8.9 Percentage of participants Interval 5.3 to 12.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 8	19.2 Percentage of participants Interval 14.6 to 23.8	17.8 Percentage of participants Interval 13.1 to 22.6	14.3 Percentage of participants Interval 9.9 to 18.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 12	22.2 Percentage of participants Interval 17.2 to 27.1	24.2 Percentage of participants Interval 19.0 to 29.5	15.7 Percentage of participants Interval 11.1 to 20.3
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 20	27.7 Percentage of participants Interval 22.2 to 33.3	26.2 Percentage of participants Interval 20.7 to 31.6	26.5 Percentage of participants Interval 20.8 to 32.2

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. At each timepoint, only participants with non-missing, valid assessments were included in the analysis.

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 20	53.7 Percentage of participants Interval 47.5 to 59.9	51.5 Percentage of participants Interval 45.1 to 57.9	44.9 Percentage of participants Interval 38.4 to 51.4
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 32	59.6 Percentage of participants Interval 53.1 to 66.0	53.1 Percentage of participants Interval 46.5 to 59.7	59.0 Percentage of participants Interval 52.2 to 65.9
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 36	66.3 Percentage of participants Interval 60.0 to 72.5	55.8 Percentage of participants Interval 49.1 to 62.5	59.0 Percentage of participants Interval 52.1 to 65.9
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 40	59.7 Percentage of participants Interval 53.1 to 66.4	54.5 Percentage of participants Interval 47.7 to 61.4	55.5 Percentage of participants Interval 48.7 to 62.4
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 52	58.8 Percentage of participants Interval 52.2 to 65.3	61.0 Percentage of participants Interval 54.2 to 67.8	60.0 Percentage of participants Interval 53.1 to 66.8
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 56	62.9 Percentage of participants Interval 56.5 to 69.3	60.1 Percentage of participants Interval 53.4 to 66.8	65.0 Percentage of participants Interval 58.3 to 71.7
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 76	66.8 Percentage of participants Interval 60.5 to 73.0	66.2 Percentage of participants Interval 59.6 to 72.9	61.8 Percentage of participants Interval 54.8 to 68.9
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 88	60.9 Percentage of participants Interval 54.3 to 67.6	61.9 Percentage of participants Interval 55.1 to 68.7	60.2 Percentage of participants Interval 53.2 to 67.3
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 92	65.1 Percentage of participants Interval 58.7 to 71.5	65.0 Percentage of participants Interval 58.2 to 71.7	63.2 Percentage of participants Interval 56.2 to 70.2
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 96	60.6 Percentage of participants Interval 54.0 to 67.1	63.8 Percentage of participants Interval 56.9 to 70.6	58.8 Percentage of participants Interval 51.5 to 66.0
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 100	62.4 Percentage of participants Interval 56.0 to 68.8	64.8 Percentage of participants Interval 58.0 to 71.6	64.0 Percentage of participants Interval 57.3 to 70.7
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 16	47.8 Percentage of participants Interval 41.4 to 54.1	49.8 Percentage of participants Interval 43.5 to 56.2	43.8 Percentage of participants Interval 37.3 to 50.3
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 4	32.0 Percentage of participants Interval 26.3 to 37.7	29.2 Percentage of participants Interval 23.5 to 35.0	25.2 Percentage of participants Interval 19.7 to 30.7
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 8	37.2 Percentage of participants Interval 31.3 to 43.1	43.9 Percentage of participants Interval 37.7 to 50.2	31.1 Percentage of participants Interval 25.2 to 37.1
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 12	46.5 Percentage of participants Interval 40.3 to 52.6	48.9 Percentage of participants Interval 42.6 to 55.2	36.9 Percentage of participants Interval 30.8 to 43.1
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 28	56.6 Percentage of participants Interval 50.3 to 62.9	57.4 Percentage of participants Interval 50.8 to 63.9	55.3 Percentage of participants Interval 48.6 to 61.9
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 24	57.9 Percentage of participants Interval 51.7 to 64.2	49.9 Percentage of participants Interval 43.5 to 56.3	57.6 Percentage of participants Interval 51.1 to 64.1
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 44	59.2 Percentage of participants Interval 52.7 to 65.7	58.1 Percentage of participants Interval 51.3 to 64.8	55.0 Percentage of participants Interval 48.1 to 61.9
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 48	58.5 Percentage of participants Interval 52.0 to 65.0	62.6 Percentage of participants Interval 56.0 to 69.2	57.1 Percentage of participants Interval 50.2 to 64.0
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 60	63.4 Percentage of participants Interval 56.9 to 69.9	61.3 Percentage of participants Interval 54.5 to 68.0	61.5 Percentage of participants Interval 54.7 to 68.2
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 64	59.8 Percentage of participants Interval 53.3 to 66.2	59.7 Percentage of participants Interval 53.0 to 66.4	67.7 Percentage of participants Interval 61.1 to 74.3
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 68	60.7 Percentage of participants Interval 54.2 to 67.2	60.6 Percentage of participants Interval 53.9 to 67.3	64.1 Percentage of participants Interval 57.4 to 70.8
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 72	62.5 Percentage of participants Interval 56.0 to 69.0	56.7 Percentage of participants Interval 49.8 to 63.7	62.6 Percentage of participants Interval 55.8 to 69.5
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 80	62.4 Percentage of participants Interval 56.0 to 68.8	62.8 Percentage of participants Interval 56.0 to 69.6	66.7 Percentage of participants Interval 59.8 to 73.5
Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 84	65.3 Percentage of participants Interval 59.0 to 71.6	67.1 Percentage of participants Interval 60.5 to 73.6	63.2 Percentage of participants Interval 56.3 to 70.1

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. At each timepoint, only participants with non-missing, valid assessments were included in the analysis.

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 4	63.1 Percentage of participants Interval 57.1 to 69.1	62.8 Percentage of participants Interval 56.7 to 68.9	53.8 Percentage of participants Interval 47.5 to 60.2
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 12	75.4 Percentage of participants Interval 69.9 to 80.8	77.0 Percentage of participants Interval 71.6 to 82.4	72.7 Percentage of participants Interval 66.9 to 78.4
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 16	81.3 Percentage of participants Interval 76.3 to 86.3	79.3 Percentage of participants Interval 74.1 to 84.5	75.6 Percentage of participants Interval 70.0 to 81.3
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 24	82.9 Percentage of participants Interval 78.1 to 87.7	71.4 Percentage of participants Interval 65.5 to 77.2	81.7 Percentage of participants Interval 76.6 to 86.8
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 60	80.5 Percentage of participants Interval 75.2 to 85.8	80.0 Percentage of participants Interval 74.5 to 85.5	81.0 Percentage of participants Interval 75.5 to 86.4
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 64	80.2 Percentage of participants Interval 74.9 to 85.6	80.3 Percentage of participants Interval 74.8 to 85.7	80.7 Percentage of participants Interval 75.1 to 86.3
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 68	78.3 Percentage of participants Interval 72.6 to 83.9	79.7 Percentage of participants Interval 74.1 to 85.2	82.0 Percentage of participants Interval 76.5 to 87.5
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 72	77.3 Percentage of participants Interval 71.6 to 82.9	80.9 Percentage of participants Interval 75.4 to 86.5	81.5 Percentage of participants Interval 76.0 to 87.0
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 76	78.0 Percentage of participants Interval 72.4 to 83.6	83.8 Percentage of participants Interval 78.6 to 88.9	79.5 Percentage of participants Interval 73.7 to 85.4
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 88	80.7 Percentage of participants Interval 75.4 to 86.1	80.6 Percentage of participants Interval 74.9 to 86.2	77.9 Percentage of participants Interval 71.8 to 83.9
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 92	82.1 Percentage of participants Interval 76.8 to 87.3	82.5 Percentage of participants Interval 77.2 to 87.9	80.5 Percentage of participants Interval 74.8 to 86.3
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 96	76.9 Percentage of participants Interval 71.2 to 82.5	82.4 Percentage of participants Interval 76.9 to 87.8	82.7 Percentage of participants Interval 77.1 to 88.3
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 8	70.5 Percentage of participants Interval 64.8 to 76.2	70.4 Percentage of participants Interval 64.6 to 76.2	63.4 Percentage of participants Interval 57.2 to 69.6
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 20	79.3 Percentage of participants Interval 74.0 to 84.6	78.2 Percentage of participants Interval 72.9 to 83.5	79.0 Percentage of participants Interval 73.6 to 84.3
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 28	81.7 Percentage of participants Interval 76.6 to 86.7	80.0 Percentage of participants Interval 74.8 to 85.3	76.9 Percentage of participants Interval 71.2 to 82.5
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 32	77.6 Percentage of participants Interval 72.0 to 83.1	83.7 Percentage of participants Interval 78.8 to 88.7	80.0 Percentage of participants Interval 74.4 to 85.6
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 36	82.9 Percentage of participants Interval 77.9 to 88.0	79.6 Percentage of participants Interval 74.1 to 85.1	80.5 Percentage of participants Interval 74.9 to 86.1
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 40	85.3 Percentage of participants Interval 80.5 to 90.1	80.0 Percentage of participants Interval 74.5 to 85.6	77.1 Percentage of participants Interval 71.3 to 82.8
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 44	82.5 Percentage of participants Interval 77.4 to 87.6	80.8 Percentage of participants Interval 75.4 to 86.2	81.4 Percentage of participants Interval 76.0 to 86.8
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 48	80.0 Percentage of participants Interval 74.6 to 85.4	80.8 Percentage of participants Interval 75.4 to 86.2	79.5 Percentage of participants Interval 73.8 to 85.2
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 52	75.3 Percentage of participants Interval 69.5 to 81.1	82.3 Percentage of participants Interval 77.1 to 87.6	78.7 Percentage of participants Interval 72.9 to 84.4
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 56	81.2 Percentage of participants Interval 75.9 to 86.4	81.9 Percentage of participants Interval 76.6 to 87.1	84.0 Percentage of participants Interval 78.9 to 89.2
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 80	80.5 Percentage of participants Interval 75.2 to 85.8	80.0 Percentage of participants Interval 74.3 to 85.7	82.0 Percentage of participants Interval 76.3 to 87.7
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 84	83.0 Percentage of participants Interval 78.0 to 87.9	81.8 Percentage of participants Interval 76.4 to 87.3	78.6 Percentage of participants Interval 72.6 to 84.6
Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 100	78.2 Percentage of participants Interval 72.6 to 83.9	85.7 Percentage of participants Interval 80.8 to 90.7	80.0 Percentage of participants Interval 74.3 to 85.8

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. At each timepoint, only participants with non-missing, valid assessments were included in the analysis.

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 8	93.3 Percentage of participants Interval 90.2 to 96.5	93.1 Percentage of participants Interval 89.9 to 96.4	91.4 Percentage of participants Interval 87.8 to 95.0
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 12	96.2 Percentage of participants Interval 93.7 to 98.6	92.8 Percentage of participants Interval 89.4 to 96.1	93.5 Percentage of participants Interval 90.4 to 96.6
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 16	94.7 Percentage of participants Interval 91.9 to 97.6	94.5 Percentage of participants Interval 91.6 to 97.4	91.5 Percentage of participants Interval 87.8 to 95.1
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 20	92.5 Percentage of participants Interval 89.1 to 95.9	92.1 Percentage of participants Interval 88.6 to 95.6	94.2 Percentage of participants Interval 91.2 to 97.2
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 24	93.4 Percentage of participants Interval 90.2 to 96.6	89.0 Percentage of participants Interval 85.0 to 93.1	94.0 Percentage of participants Interval 90.9 to 97.1
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 28	94.2 Percentage of participants Interval 91.1 to 97.2	92.6 Percentage of participants Interval 89.1 to 96.1	90.9 Percentage of participants Interval 87.0 to 94.8
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 32	94.2 Percentage of participants Interval 91.0 to 97.3	91.4 Percentage of participants Interval 87.7 to 95.2	92.3 Percentage of participants Interval 88.5 to 96.0
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 36	93.7 Percentage of participants Interval 90.4 to 97.0	89.4 Percentage of participants Interval 85.2 to 93.6	93.1 Percentage of participants Interval 89.5 to 96.7
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 44	93.4 Percentage of participants Interval 90.0 to 96.7	91.6 Percentage of participants Interval 87.8 to 95.4	91.8 Percentage of participants Interval 88.0 to 95.6
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 48	91.9 Percentage of participants Interval 88.2 to 95.6	93.1 Percentage of participants Interval 89.7 to 96.6	95.5 Percentage of participants Interval 92.6 to 98.4
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 52	89.5 Percentage of participants Interval 85.4 to 93.6	90.9 Percentage of participants Interval 87.0 to 94.9	89.8 Percentage of participants Interval 85.6 to 94.0
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 64	92.6 Percentage of participants Interval 89.1 to 96.1	92.4 Percentage of participants Interval 88.7 to 96.1	92.0 Percentage of participants Interval 88.1 to 95.9
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 68	93.4 Percentage of participants Interval 90.0 to 96.8	91.8 Percentage of participants Interval 88.0 to 95.6	92.0 Percentage of participants Interval 88.1 to 95.8
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 76	90.8 Percentage of participants Interval 86.8 to 94.8	91.6 Percentage of participants Interval 87.8 to 95.5	86.8 Percentage of participants Interval 81.8 to 91.7
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 84	92.2 Percentage of participants Interval 88.5 to 95.8	92.5 Percentage of participants Interval 88.9 to 96.1	87.4 Percentage of participants Interval 82.6 to 92.3
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 88	88.8 Percentage of participants Interval 84.5 to 93.2	89.2 Percentage of participants Interval 84.7 to 93.7	85.6 Percentage of participants Interval 80.4 to 90.7
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 4	90.9 Percentage of participants Interval 87.3 to 94.5	90.2 Percentage of participants Interval 86.5 to 94.0	86.3 Percentage of participants Interval 81.9 to 90.7
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 40	93.6 Percentage of participants Interval 90.3 to 97.0	92.5 Percentage of participants Interval 88.9 to 96.2	91.0 Percentage of participants Interval 87.0 to 94.9
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 56	92.7 Percentage of participants Interval 89.2 to 96.3	90.9 Percentage of participants Interval 86.9 to 94.9	91.7 Percentage of participants Interval 87.8 to 95.6
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 60	93.5 Percentage of participants Interval 90.1 to 96.9	91.9 Percentage of participants Interval 88.2 to 95.7	89.9 Percentage of participants Interval 85.7 to 94.1
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 72	92.0 Percentage of participants Interval 88.4 to 95.6	89.3 Percentage of participants Interval 84.9 to 93.7	88.7 Percentage of participants Interval 84.1 to 93.2
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 80	90.7 Percentage of participants Interval 86.7 to 94.7	90.1 Percentage of participants Interval 85.8 to 94.3	89.5 Percentage of participants Interval 85.0 to 94.0
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 92	90.5 Percentage of participants Interval 86.5 to 94.6	91.0 Percentage of participants Interval 86.9 to 95.1	88.8 Percentage of participants Interval 84.2 to 93.4
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 96	87.2 Percentage of participants Interval 82.6 to 91.7	90.3 Percentage of participants Interval 86.1 to 94.6	90.1 Percentage of participants Interval 85.7 to 94.6
Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 100	86.1 Percentage of participants Interval 81.4 to 90.8	92.0 Percentage of participants Interval 88.1 to 95.9	87.8 Percentage of participants Interval 83.1 to 92.6

SECONDARY outcome

Timeframe: Baseline, average of Weeks 48, 52, and 56

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=276 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=276 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=271 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population Avoiding a Loss of ≥15 Letters	98.6 Percentage of participants Interval 97.2 to 100.0	98.9 Percentage of participants Interval 97.6 to 100.0	98.1 Percentage of participants Interval 96.5 to 99.7
Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population Avoiding a Loss of ≥10 Letters	98.2 Percentage of participants Interval 96.6 to 99.8	98.1 Percentage of participants Interval 96.5 to 99.7	96.3 Percentage of participants Interval 94.1 to 98.5
Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population Avoiding a Loss of ≥5 Letters	96.7 Percentage of participants Interval 94.7 to 98.8	96.3 Percentage of participants Interval 94.1 to 98.5	95.2 Percentage of participants Interval 92.7 to 97.7

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 20	99.3 Percentage of participants Interval 98.4 to 100.0	99.6 Percentage of participants Interval 99.0 to 100.0	99.3 Percentage of participants Interval 98.4 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 4	100.0 Percentage of participants Interval 100.0 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 8	100.0 Percentage of participants Interval 100.0 to 100.0	99.3 Percentage of participants Interval 98.4 to 100.0	99.7 Percentage of participants Interval 99.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 12	100.0 Percentage of participants Interval 100.0 to 100.0	99.7 Percentage of participants Interval 99.0 to 100.0	99.3 Percentage of participants Interval 98.5 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 16	100.0 Percentage of participants Interval 100.0 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	99.7 Percentage of participants Interval 99.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 24	100.0 Percentage of participants Interval 100.0 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	99.6 Percentage of participants Interval 98.9 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 28	99.7 Percentage of participants Interval 99.0 to 100.0	99.6 Percentage of participants Interval 99.0 to 100.0	99.3 Percentage of participants Interval 98.2 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 32	100.0 Percentage of participants Interval 100.0 to 100.0	99.3 Percentage of participants Interval 98.3 to 100.0	99.6 Percentage of participants Interval 98.8 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 36	99.2 Percentage of participants Interval 98.2 to 100.0	99.6 Percentage of participants Interval 98.8 to 100.0	99.2 Percentage of participants Interval 98.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 40	99.3 Percentage of participants Interval 98.2 to 100.0	99.6 Percentage of participants Interval 98.8 to 100.0	98.8 Percentage of participants Interval 97.5 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 44	98.9 Percentage of participants Interval 97.7 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	98.8 Percentage of participants Interval 97.5 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 48	98.1 Percentage of participants Interval 96.5 to 99.7	99.3 Percentage of participants Interval 98.3 to 100.0	98.4 Percentage of participants Interval 96.9 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 52	98.1 Percentage of participants Interval 96.5 to 99.7	98.4 Percentage of participants Interval 96.8 to 99.9	97.2 Percentage of participants Interval 95.2 to 99.2
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 56	98.5 Percentage of participants Interval 97.0 to 100.0	98.4 Percentage of participants Interval 96.9 to 99.9	98.4 Percentage of participants Interval 96.9 to 99.9
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 60	98.5 Percentage of participants Interval 97.0 to 99.9	99.2 Percentage of participants Interval 98.1 to 100.0	98.1 Percentage of participants Interval 96.4 to 99.7
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 64	97.7 Percentage of participants Interval 95.8 to 99.5	98.8 Percentage of participants Interval 97.5 to 100.0	98.8 Percentage of participants Interval 97.4 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 68	98.0 Percentage of participants Interval 96.3 to 99.7	98.8 Percentage of participants Interval 97.5 to 100.0	99.1 Percentage of participants Interval 98.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 72	98.8 Percentage of participants Interval 97.5 to 100.0	98.8 Percentage of participants Interval 97.5 to 100.0	97.2 Percentage of participants Interval 95.1 to 99.2
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 76	98.0 Percentage of participants Interval 96.3 to 99.7	98.0 Percentage of participants Interval 96.3 to 99.7	96.6 Percentage of participants Interval 94.4 to 98.9
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 80	96.9 Percentage of participants Interval 94.8 to 99.0	99.1 Percentage of participants Interval 98.0 to 100.0	97.6 Percentage of participants Interval 95.7 to 99.5
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 84	98.1 Percentage of participants Interval 96.5 to 99.7	99.1 Percentage of participants Interval 98.0 to 100.0	97.1 Percentage of participants Interval 95.0 to 99.2
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 88	97.2 Percentage of participants Interval 95.2 to 99.2	97.9 Percentage of participants Interval 96.1 to 99.7	97.1 Percentage of participants Interval 95.0 to 99.2
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 92	97.4 Percentage of participants Interval 95.5 to 99.3	98.3 Percentage of participants Interval 96.6 to 99.9	97.1 Percentage of participants Interval 95.0 to 99.2
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 96	96.6 Percentage of participants Interval 94.4 to 98.8	97.8 Percentage of participants Interval 95.9 to 99.7	97.4 Percentage of participants Interval 95.3 to 99.4
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 100	97.0 Percentage of participants Interval 94.9 to 99.0	98.4 Percentage of participants Interval 96.8 to 99.9	96.3 Percentage of participants Interval 93.9 to 98.7

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 4	100.0 Percentage of participants Interval 100.0 to 100.0	99.4 Percentage of participants Interval 98.5 to 100.0	98.7 Percentage of participants Interval 97.5 to 99.9
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 8	100.0 Percentage of participants Interval 100.0 to 100.0	99.0 Percentage of participants Interval 97.9 to 100.0	98.4 Percentage of participants Interval 97.0 to 99.8
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 12	100.0 Percentage of participants Interval 100.0 to 100.0	99.3 Percentage of participants Interval 98.4 to 100.0	98.7 Percentage of participants Interval 97.4 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 16	99.3 Percentage of participants Interval 98.4 to 100.0	99.7 Percentage of participants Interval 99.0 to 100.0	99.3 Percentage of participants Interval 98.4 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 20	98.6 Percentage of participants Interval 97.3 to 100.0	99.3 Percentage of participants Interval 98.4 to 100.0	99.0 Percentage of participants Interval 97.8 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 24	99.7 Percentage of participants Interval 99.0 to 100.0	99.3 Percentage of participants Interval 98.4 to 100.0	98.6 Percentage of participants Interval 97.2 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 28	99.0 Percentage of participants Interval 97.8 to 100.0	98.6 Percentage of participants Interval 97.2 to 100.0	97.4 Percentage of participants Interval 95.6 to 99.3
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 32	98.5 Percentage of participants Interval 97.0 to 99.9	98.5 Percentage of participants Interval 97.1 to 99.9	99.2 Percentage of participants Interval 98.1 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 36	98.9 Percentage of participants Interval 97.6 to 100.0	99.2 Percentage of participants Interval 98.2 to 100.0	98.4 Percentage of participants Interval 96.9 to 99.9
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 40	99.3 Percentage of participants Interval 98.2 to 100.0	98.5 Percentage of participants Interval 97.0 to 99.9	97.7 Percentage of participants Interval 95.9 to 99.5
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 44	98.2 Percentage of participants Interval 96.6 to 99.8	99.2 Percentage of participants Interval 98.2 to 100.0	97.3 Percentage of participants Interval 95.4 to 99.3
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 48	97.8 Percentage of participants Interval 96.0 to 99.5	98.5 Percentage of participants Interval 97.1 to 99.9	98.1 Percentage of participants Interval 96.4 to 99.7
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 52	97.0 Percentage of participants Interval 95.0 to 99.0	96.8 Percentage of participants Interval 94.6 to 99.0	95.3 Percentage of participants Interval 92.8 to 97.9
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 56	98.1 Percentage of participants Interval 96.5 to 99.7	96.5 Percentage of participants Interval 94.3 to 98.7	97.2 Percentage of participants Interval 95.2 to 99.2
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 60	97.3 Percentage of participants Interval 95.4 to 99.3	98.1 Percentage of participants Interval 96.4 to 99.7	96.9 Percentage of participants Interval 94.8 to 99.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 64	96.5 Percentage of participants Interval 94.2 to 98.7	98.1 Percentage of participants Interval 96.4 to 99.7	98.0 Percentage of participants Interval 96.3 to 99.7
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 68	97.6 Percentage of participants Interval 95.8 to 99.5	98.4 Percentage of participants Interval 96.9 to 100.0	96.9 Percentage of participants Interval 94.7 to 99.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 72	98.0 Percentage of participants Interval 96.4 to 99.7	97.6 Percentage of participants Interval 95.7 to 99.5	96.0 Percentage of participants Interval 93.6 to 98.4
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 76	95.6 Percentage of participants Interval 93.1 to 98.1	97.6 Percentage of participants Interval 95.7 to 99.5	95.9 Percentage of participants Interval 93.4 to 98.4
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 80	96.2 Percentage of participants Interval 93.8 to 98.5	97.6 Percentage of participants Interval 95.9 to 99.5	96.3 Percentage of participants Interval 94.0 to 98.7
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 84	97.0 Percentage of participants Interval 95.0 to 99.0	99.1 Percentage of participants Interval 98.0 to 100.0	95.5 Percentage of participants Interval 93.0 to 98.1
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 88	95.6 Percentage of participants Interval 93.1 to 98.1	96.7 Percentage of participants Interval 94.5 to 98.9	95.0 Percentage of participants Interval 92.3 to 97.7
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 92	96.5 Percentage of participants Interval 94.3 to 98.7	97.5 Percentage of participants Interval 95.5 to 99.5	95.9 Percentage of participants Interval 93.3 to 98.4
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 96	94.3 Percentage of participants Interval 91.5 to 97.1	96.6 Percentage of participants Interval 94.3 to 98.9	96.9 Percentage of participants Interval 94.7 to 99.2
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 100	94.6 Percentage of participants Interval 91.8 to 97.3	97.1 Percentage of participants Interval 95.1 to 99.2	94.3 Percentage of participants Interval 91.5 to 97.2

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 4	97.4 Percentage of participants Interval 95.6 to 99.1	96.4 Percentage of participants Interval 94.4 to 98.4	97.7 Percentage of participants Interval 96.1 to 99.4
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 8	98.7 Percentage of participants Interval 97.5 to 100.0	97.3 Percentage of participants Interval 95.5 to 99.1	96.4 Percentage of participants Interval 94.4 to 98.5
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 12	98.0 Percentage of participants Interval 96.4 to 99.6	98.4 Percentage of participants Interval 97.0 to 99.8	98.0 Percentage of participants Interval 96.5 to 99.6
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 16	98.6 Percentage of participants Interval 97.3 to 100.0	98.7 Percentage of participants Interval 97.4 to 100.0	97.3 Percentage of participants Interval 95.5 to 99.1
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 20	97.2 Percentage of participants Interval 95.4 to 99.1	97.3 Percentage of participants Interval 95.4 to 99.1	96.9 Percentage of participants Interval 95.0 to 98.9
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 24	96.9 Percentage of participants Interval 94.9 to 98.9	96.6 Percentage of participants Interval 94.6 to 98.7	96.9 Percentage of participants Interval 94.9 to 98.9
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 28	97.6 Percentage of participants Interval 95.8 to 99.3	96.1 Percentage of participants Interval 93.9 to 98.4	96.4 Percentage of participants Interval 94.2 to 98.6
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 32	97.4 Percentage of participants Interval 95.5 to 99.3	97.5 Percentage of participants Interval 95.6 to 99.3	96.6 Percentage of participants Interval 94.4 to 98.8
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 36	97.3 Percentage of participants Interval 95.4 to 99.3	97.7 Percentage of participants Interval 96.0 to 99.5	96.2 Percentage of participants Interval 93.9 to 98.5
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 40	95.8 Percentage of participants Interval 93.4 to 98.2	97.7 Percentage of participants Interval 95.9 to 99.5	95.2 Percentage of participants Interval 92.6 to 97.7
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 44	96.7 Percentage of participants Interval 94.6 to 98.8	95.8 Percentage of participants Interval 93.4 to 98.2	95.2 Percentage of participants Interval 92.6 to 97.7
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 48	96.7 Percentage of participants Interval 94.5 to 98.8	96.9 Percentage of participants Interval 94.9 to 99.0	96.6 Percentage of participants Interval 94.4 to 98.8
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 52	95.9 Percentage of participants Interval 93.5 to 98.3	94.9 Percentage of participants Interval 92.2 to 97.6	94.2 Percentage of participants Interval 91.4 to 97.0
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 56	96.2 Percentage of participants Interval 93.8 to 98.5	95.0 Percentage of participants Interval 92.4 to 97.6	96.0 Percentage of participants Interval 93.7 to 98.4
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 60	96.2 Percentage of participants Interval 93.8 to 98.5	97.0 Percentage of participants Interval 94.9 to 99.0	94.0 Percentage of participants Interval 91.2 to 96.8
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 64	96.1 Percentage of participants Interval 93.8 to 98.5	96.1 Percentage of participants Interval 93.8 to 98.4	95.7 Percentage of participants Interval 93.2 to 98.2
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 68	96.4 Percentage of participants Interval 94.1 to 98.7	96.1 Percentage of participants Interval 93.8 to 98.5	94.8 Percentage of participants Interval 92.1 to 97.6
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 72	95.3 Percentage of participants Interval 92.7 to 97.9	94.4 Percentage of participants Interval 91.5 to 97.2	93.3 Percentage of participants Interval 90.3 to 96.4
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 76	94.8 Percentage of participants Interval 92.0 to 97.5	95.2 Percentage of participants Interval 92.6 to 97.8	92.6 Percentage of participants Interval 89.4 to 95.9
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 80	93.4 Percentage of participants Interval 90.4 to 96.4	94.0 Percentage of participants Interval 91.1 to 96.9	94.0 Percentage of participants Interval 91.0 to 96.9
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 84	95.8 Percentage of participants Interval 93.4 to 98.2	97.2 Percentage of participants Interval 95.1 to 99.2	92.8 Percentage of participants Interval 89.6 to 96.0
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 88	92.6 Percentage of participants Interval 89.4 to 95.8	94.7 Percentage of participants Interval 91.9 to 97.5	89.8 Percentage of participants Interval 86.0 to 93.5
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 92	92.7 Percentage of participants Interval 89.5 to 95.8	96.7 Percentage of participants Interval 94.4 to 98.9	93.8 Percentage of participants Interval 90.8 to 96.8
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 96	92.3 Percentage of participants Interval 89.1 to 95.5	95.0 Percentage of participants Interval 92.3 to 97.8	94.9 Percentage of participants Interval 92.0 to 97.7
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population Week 100	88.9 Percentage of participants Interval 85.1 to 92.6	96.4 Percentage of participants Interval 94.1 to 98.6	91.1 Percentage of participants Interval 87.6 to 94.6

SECONDARY outcome

Timeframe: Baseline, average of Weeks 48, 52, and 56

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=215 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=212 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=200 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population Avoiding a Loss of ≥15 Letters	98.1 Percentage of participants Interval 96.3 to 99.9	99.0 Percentage of participants Interval 97.7 to 100.0	97.9 Percentage of participants Interval 96.0 to 99.9
Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population Avoiding a Loss of ≥10 Letters	97.7 Percentage of participants Interval 95.7 to 99.7	98.6 Percentage of participants Interval 97.0 to 100.0	96.5 Percentage of participants Interval 93.9 to 99.0
Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population Avoiding a Loss of ≥5 Letters	95.8 Percentage of participants Interval 93.1 to 98.5	96.2 Percentage of participants Interval 93.6 to 98.8	95.0 Percentage of participants Interval 91.9 to 98.0

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. At each timepoint, only participants with non-missing, valid assessments were included in the analysis.

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 64	97.0 Percentage of participants Interval 94.6 to 99.4	98.4 Percentage of participants Interval 96.7 to 100.0	98.4 Percentage of participants Interval 96.5 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 68	97.4 Percentage of participants Interval 95.2 to 99.6	98.4 Percentage of participants Interval 96.7 to 100.0	98.9 Percentage of participants Interval 97.3 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 4	100.0 Percentage of participants Interval 100.0 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 8	100.0 Percentage of participants Interval 100.0 to 100.0	99.6 Percentage of participants Interval 98.8 to 100.0	99.6 Percentage of participants Interval 98.7 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 12	100.0 Percentage of participants Interval 100.0 to 100.0	99.6 Percentage of participants Interval 98.7 to 100.0	99.6 Percentage of participants Interval 98.7 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 16	100.0 Percentage of participants Interval 100.0 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	99.6 Percentage of participants Interval 98.7 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 20	99.1 Percentage of participants Interval 97.9 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	99.1 Percentage of participants Interval 97.9 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 24	100.0 Percentage of participants Interval 100.0 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	99.5 Percentage of participants Interval 98.6 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 28	99.6 Percentage of participants Interval 98.7 to 100.0	99.5 Percentage of participants Interval 98.6 to 100.0	99.0 Percentage of participants Interval 97.6 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 32	100.0 Percentage of participants Interval 100.0 to 100.0	99.0 Percentage of participants Interval 97.7 to 100.0	99.5 Percentage of participants Interval 98.4 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 36	99.0 Percentage of participants Interval 97.6 to 100.0	99.5 Percentage of participants Interval 98.4 to 100.0	98.9 Percentage of participants Interval 97.3 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 40	99.0 Percentage of participants Interval 97.7 to 100.0	99.5 Percentage of participants Interval 98.4 to 100.0	98.4 Percentage of participants Interval 96.6 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 44	98.6 Percentage of participants Interval 97.0 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	98.9 Percentage of participants Interval 97.5 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 48	97.6 Percentage of participants Interval 95.5 to 99.7	99.0 Percentage of participants Interval 97.7 to 100.0	98.4 Percentage of participants Interval 96.6 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 52	97.6 Percentage of participants Interval 95.5 to 99.7	98.4 Percentage of participants Interval 96.6 to 100.0	96.8 Percentage of participants Interval 94.3 to 99.3
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 56	98.1 Percentage of participants Interval 96.2 to 99.9	98.5 Percentage of participants Interval 96.7 to 100.0	98.4 Percentage of participants Interval 96.7 to 100.0
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 60	98.0 Percentage of participants Interval 96.1 to 99.9	99.0 Percentage of participants Interval 97.5 to 100.0	97.4 Percentage of participants Interval 95.2 to 99.6
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 72	98.5 Percentage of participants Interval 96.8 to 100.0	98.4 Percentage of participants Interval 96.6 to 100.0	96.2 Percentage of participants Interval 93.4 to 98.9
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 76	97.4 Percentage of participants Interval 95.2 to 99.6	97.9 Percentage of participants Interval 95.9 to 99.9	95.5 Percentage of participants Interval 92.4 to 98.5
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 80	96.6 Percentage of participants Interval 94.1 to 99.1	98.8 Percentage of participants Interval 97.3 to 100.0	96.7 Percentage of participants Interval 94.1 to 99.3
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 84	98.0 Percentage of participants Interval 96.1 to 99.9	99.5 Percentage of participants Interval 98.4 to 100.0	96.1 Percentage of participants Interval 93.3 to 98.9
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 88	97.5 Percentage of participants Interval 95.3 to 99.6	97.7 Percentage of participants Interval 95.5 to 99.9	96.1 Percentage of participants Interval 93.2 to 98.9
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 92	97.0 Percentage of participants Interval 94.7 to 99.3	98.3 Percentage of participants Interval 96.4 to 100.0	96.1 Percentage of participants Interval 93.2 to 98.9
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 96	96.1 Percentage of participants Interval 93.4 to 98.7	98.9 Percentage of participants Interval 97.3 to 100.0	97.1 Percentage of participants Interval 94.6 to 99.6
Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 100	97.1 Percentage of participants Interval 94.8 to 99.4	98.4 Percentage of participants Interval 96.6 to 100.0	96.1 Percentage of participants Interval 93.3 to 98.9

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. At each timepoint, only participants with non-missing, valid assessments were included in the analysis.

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 4	100.0 Percentage of participants Interval 100.0 to 100.0	99.2 Percentage of participants Interval 98.0 to 100.0	99.6 Percentage of participants Interval 98.7 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 68	96.9 Percentage of participants Interval 94.6 to 99.3	97.9 Percentage of participants Interval 95.9 to 99.9	96.8 Percentage of participants Interval 94.3 to 99.3
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 8	100.0 Percentage of participants Interval 100.0 to 100.0	99.6 Percentage of participants Interval 98.8 to 100.0	98.3 Percentage of participants Interval 96.6 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 12	100.0 Percentage of participants Interval 100.0 to 100.0	99.6 Percentage of participants Interval 98.7 to 100.0	99.1 Percentage of participants Interval 97.9 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 16	99.1 Percentage of participants Interval 97.9 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	99.1 Percentage of participants Interval 97.9 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 20	98.3 Percentage of participants Interval 96.6 to 99.9	100.0 Percentage of participants Interval 100.0 to 100.0	99.1 Percentage of participants Interval 97.9 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 24	99.6 Percentage of participants Interval 98.7 to 100.0	99.1 Percentage of participants Interval 97.9 to 100.0	99.1 Percentage of participants Interval 97.8 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 28	98.7 Percentage of participants Interval 97.2 to 100.0	98.6 Percentage of participants Interval 97.1 to 100.0	98.0 Percentage of participants Interval 96.1 to 99.9
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 32	98.0 Percentage of participants Interval 96.1 to 99.9	98.1 Percentage of participants Interval 96.2 to 99.9	99.5 Percentage of participants Interval 98.4 to 100.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 36	98.5 Percentage of participants Interval 96.8 to 100.0	99.0 Percentage of participants Interval 97.6 to 100.0	97.9 Percentage of participants Interval 95.8 to 99.9
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 40	99.0 Percentage of participants Interval 97.7 to 100.0	97.9 Percentage of participants Interval 95.9 to 99.9	96.9 Percentage of participants Interval 94.5 to 99.3
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 44	97.6 Percentage of participants Interval 95.6 to 99.7	99.0 Percentage of participants Interval 97.6 to 100.0	97.4 Percentage of participants Interval 95.2 to 99.6
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 48	97.1 Percentage of participants Interval 94.9 to 99.4	98.5 Percentage of participants Interval 96.9 to 100.0	97.9 Percentage of participants Interval 95.9 to 99.9
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 52	96.2 Percentage of participants Interval 93.6 to 98.8	96.8 Percentage of participants Interval 94.4 to 99.3	95.3 Percentage of participants Interval 92.3 to 98.3
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 56	97.6 Percentage of participants Interval 95.5 to 99.7	96.4 Percentage of participants Interval 93.9 to 99.0	97.4 Percentage of participants Interval 95.2 to 99.6
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 60	96.5 Percentage of participants Interval 93.9 to 99.0	97.9 Percentage of participants Interval 95.9 to 99.9	96.4 Percentage of participants Interval 93.8 to 99.0
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 64	96.5 Percentage of participants Interval 94.0 to 99.1	97.4 Percentage of participants Interval 95.2 to 99.6	97.3 Percentage of participants Interval 95.0 to 99.6
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 72	98.0 Percentage of participants Interval 96.1 to 99.9	97.3 Percentage of participants Interval 95.0 to 99.6	95.1 Percentage of participants Interval 92.0 to 98.2
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 76	94.3 Percentage of participants Interval 91.1 to 97.6	97.4 Percentage of participants Interval 95.1 to 99.6	94.9 Percentage of participants Interval 91.7 to 98.2
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 80	95.6 Percentage of participants Interval 92.8 to 98.4	97.3 Percentage of participants Interval 94.9 to 99.6	95.0 Percentage of participants Interval 91.8 to 98.2
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 84	97.1 Percentage of participants Interval 94.7 to 99.4	99.5 Percentage of participants Interval 98.4 to 100.0	94.0 Percentage of participants Interval 90.5 to 97.4
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 88	95.4 Percentage of participants Interval 92.5 to 98.3	96.1 Percentage of participants Interval 93.3 to 98.9	93.9 Percentage of participants Interval 90.4 to 97.4
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 92	96.5 Percentage of participants Interval 94.0 to 99.0	97.2 Percentage of participants Interval 94.9 to 99.6	95.0 Percentage of participants Interval 91.8 to 98.2
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 96	93.6 Percentage of participants Interval 90.2 to 97.0	97.2 Percentage of participants Interval 94.8 to 99.6	96.5 Percentage of participants Interval 93.7 to 99.3
Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 100	94.6 Percentage of participants Interval 91.5 to 97.7	97.3 Percentage of participants Interval 94.9 to 99.6	93.9 Percentage of participants Interval 90.4 to 97.4

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. At each timepoint, only participants with non-missing, valid assessments were included in the analysis.

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 28	97.3 Percentage of participants Interval 95.2 to 99.4	96.8 Percentage of participants Interval 94.5 to 99.1	96.6 Percentage of participants Interval 94.1 to 99.0
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 44	95.8 Percentage of participants Interval 93.1 to 98.5	96.5 Percentage of participants Interval 93.9 to 99.0	95.9 Percentage of participants Interval 93.2 to 98.7
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 84	96.1 Percentage of participants Interval 93.4 to 98.7	96.9 Percentage of participants Interval 94.4 to 99.3	91.9 Percentage of participants Interval 87.9 to 95.8
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 4	97.5 Percentage of participants Interval 95.5 to 99.5	97.0 Percentage of participants Interval 94.9 to 99.2	98.7 Percentage of participants Interval 97.3 to 100.0
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 8	99.2 Percentage of participants Interval 98.1 to 100.0	98.3 Percentage of participants Interval 96.6 to 99.9	96.5 Percentage of participants Interval 94.2 to 98.8
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 12	98.7 Percentage of participants Interval 97.3 to 100.0	98.7 Percentage of participants Interval 97.3 to 100.0	98.3 Percentage of participants Interval 96.6 to 99.9
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 16	98.3 Percentage of participants Interval 96.6 to 99.9	98.7 Percentage of participants Interval 97.3 to 100.0	97.8 Percentage of participants Interval 95.8 to 99.7
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 20	96.5 Percentage of participants Interval 94.2 to 98.9	97.8 Percentage of participants Interval 95.9 to 99.7	97.3 Percentage of participants Interval 95.2 to 99.4
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 24	96.1 Percentage of participants Interval 93.5 to 98.6	96.5 Percentage of participants Interval 94.1 to 98.9	97.7 Percentage of participants Interval 95.7 to 99.7
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 32	96.6 Percentage of participants Interval 94.1 to 99.1	97.6 Percentage of participants Interval 95.5 to 99.7	97.4 Percentage of participants Interval 95.1 to 99.6
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 36	97.6 Percentage of participants Interval 95.4 to 99.7	98.1 Percentage of participants Interval 96.2 to 99.9	96.3 Percentage of participants Interval 93.6 to 99.0
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 40	95.6 Percentage of participants Interval 92.7 to 98.4	96.9 Percentage of participants Interval 94.5 to 99.3	94.5 Percentage of participants Interval 91.3 to 97.6
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 48	95.7 Percentage of participants Interval 93.0 to 98.5	97.5 Percentage of participants Interval 95.4 to 99.7	96.4 Percentage of participants Interval 93.8 to 99.0
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 52	94.8 Percentage of participants Interval 91.7 to 97.8	94.4 Percentage of participants Interval 91.2 to 97.6	94.3 Percentage of participants Interval 91.1 to 97.6
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 56	95.6 Percentage of participants Interval 92.9 to 98.4	94.4 Percentage of participants Interval 91.3 to 97.6	95.8 Percentage of participants Interval 93.0 to 98.6
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 60	96.0 Percentage of participants Interval 93.3 to 98.7	96.9 Percentage of participants Interval 94.6 to 99.3	94.4 Percentage of participants Interval 91.2 to 97.6
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 64	96.0 Percentage of participants Interval 93.3 to 98.7	95.8 Percentage of participants Interval 93.0 to 98.6	95.2 Percentage of participants Interval 92.2 to 98.3
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 68	95.9 Percentage of participants Interval 93.2 to 98.7	96.4 Percentage of participants Interval 93.8 to 99.0	94.6 Percentage of participants Interval 91.4 to 97.9
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 72	95.9 Percentage of participants Interval 93.2 to 98.7	94.7 Percentage of participants Interval 91.4 to 97.9	92.6 Percentage of participants Interval 88.8 to 96.3
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 76	93.8 Percentage of participants Interval 90.5 to 97.2	94.7 Percentage of participants Interval 91.5 to 97.9	91.1 Percentage of participants Interval 86.9 to 95.3
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 80	92.6 Percentage of participants Interval 89.1 to 96.2	94.2 Percentage of participants Interval 90.9 to 97.5	92.8 Percentage of participants Interval 89.0 to 96.6
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 88	91.9 Percentage of participants Interval 88.1 to 95.7	93.5 Percentage of participants Interval 89.9 to 97.0	88.3 Percentage of participants Interval 83.6 to 93.0
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 92	92.5 Percentage of participants Interval 88.9 to 96.2	96.7 Percentage of participants Interval 94.1 to 99.3	92.7 Percentage of participants Interval 88.9 to 96.5
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 96	91.5 Percentage of participants Interval 87.7 to 95.4	95.2 Percentage of participants Interval 92.1 to 98.3	94.8 Percentage of participants Interval 91.4 to 98.1
Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population Week 100	88.1 Percentage of participants Interval 83.7 to 92.5	96.8 Percentage of participants Interval 94.2 to 99.3	90.6 Percentage of participants Interval 86.4 to 94.9

SECONDARY outcome

Timeframe: Baseline, average of Weeks 48, 52, and 56

Population: ITT Population and Treatment-Naive Population. Only participants with at least one non-missing, valid assessment at Weeks 48, 52, or 56 were included in the analysis.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=276 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=276 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=271 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations ITT Population	39.1 Percentage of participants Interval 33.5 to 44.7	37.0 Percentage of participants Interval 31.5 to 42.5	32.1 Percentage of participants Interval 26.6 to 37.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations Treatment-Naive Population	39.2 Percentage of participants Interval 32.8 to 45.5	40.2 Percentage of participants Interval 33.7 to 46.6	31.5 Percentage of participants Interval 25.1 to 38.0

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 40	40.4 Percentage of participants Interval 34.7 to 46.2	33.8 Percentage of participants Interval 28.2 to 39.4	32.9 Percentage of participants Interval 27.4 to 38.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 48	41.8 Percentage of participants Interval 36.1 to 47.6	41.7 Percentage of participants Interval 36.0 to 47.4	35.7 Percentage of participants Interval 30.0 to 41.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 72	40.5 Percentage of participants Interval 34.8 to 46.2	37.7 Percentage of participants Interval 31.8 to 43.6	39.8 Percentage of participants Interval 33.9 to 45.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 92	43.6 Percentage of participants Interval 37.8 to 49.4	42.7 Percentage of participants Interval 36.7 to 48.7	42.5 Percentage of participants Interval 36.4 to 48.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 4	14.6 Percentage of participants Interval 10.8 to 18.4	13.3 Percentage of participants Interval 9.6 to 17.0	8.7 Percentage of participants Interval 5.6 to 11.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 8	20.1 Percentage of participants Interval 15.9 to 24.4	19.9 Percentage of participants Interval 15.6 to 24.3	15.3 Percentage of participants Interval 11.3 to 19.3
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 12	25.7 Percentage of participants Interval 21.1 to 30.4	25.3 Percentage of participants Interval 20.6 to 30.0	17.9 Percentage of participants Interval 13.6 to 22.1
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 16	29.1 Percentage of participants Interval 24.2 to 34.0	25.2 Percentage of participants Interval 20.5 to 30.0	24.1 Percentage of participants Interval 19.2 to 28.9
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 20	30.8 Percentage of participants Interval 25.6 to 35.9	27.7 Percentage of participants Interval 22.8 to 32.6	30.1 Percentage of participants Interval 24.9 to 35.2
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 24	37.8 Percentage of participants Interval 32.5 to 43.2	30.9 Percentage of participants Interval 25.7 to 36.0	31.3 Percentage of participants Interval 26.0 to 36.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 28	32.6 Percentage of participants Interval 27.4 to 37.8	35.0 Percentage of participants Interval 29.7 to 40.4	28.3 Percentage of participants Interval 23.1 to 33.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 32	38.8 Percentage of participants Interval 33.2 to 44.4	31.0 Percentage of participants Interval 25.8 to 36.2	33.7 Percentage of participants Interval 28.0 to 39.3
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 36	42.4 Percentage of participants Interval 36.8 to 48.1	35.6 Percentage of participants Interval 30.0 to 41.1	29.6 Percentage of participants Interval 24.1 to 35.0
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 44	39.7 Percentage of participants Interval 34.1 to 45.3	39.9 Percentage of participants Interval 34.2 to 45.7	32.1 Percentage of participants Interval 26.5 to 37.7
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 52	40.2 Percentage of participants Interval 34.5 to 45.8	41.7 Percentage of participants Interval 35.8 to 47.6	35.7 Percentage of participants Interval 29.9 to 41.4
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 56	42.6 Percentage of participants Interval 36.7 to 48.4	35.7 Percentage of participants Interval 30.1 to 41.4	43.1 Percentage of participants Interval 37.1 to 49.1
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 60	45.0 Percentage of participants Interval 39.1 to 51.0	40.6 Percentage of participants Interval 34.8 to 46.3	39.5 Percentage of participants Interval 33.7 to 45.3
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 64	44.0 Percentage of participants Interval 38.2 to 49.8	37.9 Percentage of participants Interval 32.1 to 43.7	42.1 Percentage of participants Interval 36.1 to 48.1
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 68	45.6 Percentage of participants Interval 39.7 to 51.6	40.3 Percentage of participants Interval 34.5 to 46.2	42.2 Percentage of participants Interval 36.2 to 48.2
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 76	47.7 Percentage of participants Interval 41.8 to 53.5	42.9 Percentage of participants Interval 36.8 to 49.0	42.2 Percentage of participants Interval 36.1 to 48.4
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 80	44.8 Percentage of participants Interval 39.0 to 50.5	41.9 Percentage of participants Interval 35.9 to 47.8	42.9 Percentage of participants Interval 36.8 to 49.0
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 84	43.0 Percentage of participants Interval 37.2 to 48.7	42.9 Percentage of participants Interval 36.9 to 48.9	42.4 Percentage of participants Interval 36.3 to 48.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 88	41.7 Percentage of participants Interval 36.1 to 47.4	40.0 Percentage of participants Interval 34.1 to 46.0	41.2 Percentage of participants Interval 35.1 to 47.3
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 96	42.4 Percentage of participants Interval 36.6 to 48.1	42.7 Percentage of participants Interval 36.6 to 48.7	44.9 Percentage of participants Interval 38.7 to 51.1
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population Week 100	41.8 Percentage of participants Interval 36.1 to 47.5	44.7 Percentage of participants Interval 38.6 to 50.8	43.5 Percentage of participants Interval 37.5 to 49.6

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. At each timepoint, only participants with non-missing, valid assessments were included in the analysis.

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 4	17.0 Percentage of participants Interval 12.4 to 21.6	15.2 Percentage of participants Interval 10.7 to 19.8	9.8 Percentage of participants Interval 6.0 to 13.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 20	30.4 Percentage of participants Interval 24.6 to 36.1	30.6 Percentage of participants Interval 24.8 to 36.4	31.0 Percentage of participants Interval 25.0 to 37.0
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 32	40.5 Percentage of participants Interval 34.0 to 46.9	35.4 Percentage of participants Interval 29.0 to 41.7	33.3 Percentage of participants Interval 26.7 to 39.9
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 40	41.1 Percentage of participants Interval 34.5 to 47.7	37.1 Percentage of participants Interval 30.4 to 43.7	31.5 Percentage of participants Interval 25.1 to 37.9
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 8	20.9 Percentage of participants Interval 16.1 to 25.7	22.2 Percentage of participants Interval 16.9 to 27.4	16.0 Percentage of participants Interval 11.3 to 20.7
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 12	25.6 Percentage of participants Interval 20.3 to 30.9	28.5 Percentage of participants Interval 22.9 to 34.1	19.2 Percentage of participants Interval 14.1 to 24.2
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 16	29.5 Percentage of participants Interval 23.8 to 35.2	27.9 Percentage of participants Interval 22.2 to 33.6	24.9 Percentage of participants Interval 19.2 to 30.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 24	38.2 Percentage of participants Interval 32.1 to 44.3	33.3 Percentage of participants Interval 27.3 to 39.4	32.5 Percentage of participants Interval 26.3 to 38.7
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 28	32.0 Percentage of participants Interval 26.2 to 37.8	38.5 Percentage of participants Interval 32.2 to 44.8	26.9 Percentage of participants Interval 20.9 to 32.9
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 36	44.8 Percentage of participants Interval 38.3 to 51.3	38.4 Percentage of participants Interval 31.9 to 44.8	29.5 Percentage of participants Interval 23.1 to 36.0
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 44	42.9 Percentage of participants Interval 36.4 to 49.5	42.7 Percentage of participants Interval 36.0 to 49.4	31.1 Percentage of participants Interval 24.7 to 37.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 48	41.9 Percentage of participants Interval 35.3 to 48.5	44.9 Percentage of participants Interval 38.2 to 51.6	37.5 Percentage of participants Interval 30.7 to 44.3
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 52	39.2 Percentage of participants Interval 32.8 to 45.6	43.8 Percentage of participants Interval 36.9 to 50.6	35.5 Percentage of participants Interval 28.9 to 42.2
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 56	43.1 Percentage of participants Interval 36.5 to 49.7	38.9 Percentage of participants Interval 32.2 to 45.5	43.3 Percentage of participants Interval 36.3 to 50.3
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 60	46.7 Percentage of participants Interval 39.9 to 53.5	43.6 Percentage of participants Interval 36.8 to 50.4	39.4 Percentage of participants Interval 32.6 to 46.2
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 64	46.4 Percentage of participants Interval 39.8 to 53.1	38.7 Percentage of participants Interval 32.0 to 45.3	43.0 Percentage of participants Interval 36.0 to 50.0
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 68	47.9 Percentage of participants Interval 41.1 to 54.7	42.2 Percentage of participants Interval 35.4 to 49.0	43.7 Percentage of participants Interval 36.6 to 50.7
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 72	42.1 Percentage of participants Interval 35.5 to 48.7	39.3 Percentage of participants Interval 32.5 to 46.2	40.7 Percentage of participants Interval 33.7 to 47.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 76	49.9 Percentage of participants Interval 43.3 to 56.6	43.8 Percentage of participants Interval 36.8 to 50.8	44.6 Percentage of participants Interval 37.3 to 51.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 80	46.6 Percentage of participants Interval 40.1 to 53.2	46.1 Percentage of participants Interval 39.1 to 53.1	44.6 Percentage of participants Interval 37.3 to 51.8
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 84	45.2 Percentage of participants Interval 38.6 to 51.7	45.7 Percentage of participants Interval 38.7 to 52.7	42.7 Percentage of participants Interval 35.6 to 49.9
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 88	42.7 Percentage of participants Interval 36.3 to 49.2	42.5 Percentage of participants Interval 35.5 to 49.6	41.3 Percentage of participants Interval 34.2 to 48.5
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 92	45.5 Percentage of participants Interval 38.9 to 52.1	43.9 Percentage of participants Interval 36.9 to 50.8	43.4 Percentage of participants Interval 36.3 to 50.6
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 96	43.6 Percentage of participants Interval 37.2 to 50.1	44.7 Percentage of participants Interval 37.7 to 51.8	46.7 Percentage of participants Interval 39.3 to 54.1
Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 100	44.4 Percentage of participants Interval 37.9 to 50.9	45.8 Percentage of participants Interval 38.8 to 52.9	44.1 Percentage of participants Interval 37.0 to 51.3

SECONDARY outcome

Timeframe: Baseline, average of Weeks 48, 52, and 56

Population: ITT Population and Treatment-Naive Population. Only participants with at least one non-missing, valid assessment at Weeks 48, 52, or 56 were included in the analysis.

BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥69 vs. \<69 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=276 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=276 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=271 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations ITT Population	77.1 Percentage of participants Interval 72.4 to 81.8	74.8 Percentage of participants Interval 69.9 to 79.6	71.6 Percentage of participants Interval 66.5 to 76.6
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations Treatment-Naive Population	75.7 Percentage of participants Interval 70.3 to 81.1	77.4 Percentage of participants Interval 72.2 to 82.7	72.7 Percentage of participants Interval 66.9 to 78.5

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥69 vs. \<69 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 36	79.4 Percentage of participants Interval 74.7 to 84.1	73.2 Percentage of participants Interval 68.1 to 78.2	71.8 Percentage of participants Interval 66.8 to 76.9
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 60	76.6 Percentage of participants Interval 71.6 to 81.5	75.9 Percentage of participants Interval 70.9 to 80.9	71.8 Percentage of participants Interval 66.6 to 76.9
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 84	77.2 Percentage of participants Interval 72.3 to 82.1	77.3 Percentage of participants Interval 72.5 to 82.2	73.7 Percentage of participants Interval 68.4 to 79.1
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 92	78.4 Percentage of participants Interval 73.4 to 83.3	77.4 Percentage of participants Interval 72.6 to 82.2	75.3 Percentage of participants Interval 70.0 to 80.6
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 56	79.5 Percentage of participants Interval 74.8 to 84.2	72.2 Percentage of participants Interval 67.0 to 77.4	74.9 Percentage of participants Interval 69.9 to 79.9
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 64	76.2 Percentage of participants Interval 71.4 to 81.0	71.4 Percentage of participants Interval 66.3 to 76.5	74.9 Percentage of participants Interval 69.8 to 79.9
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 68	78.0 Percentage of participants Interval 73.2 to 82.8	73.9 Percentage of participants Interval 68.9 to 78.9	74.4 Percentage of participants Interval 69.2 to 79.7
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 72	76.8 Percentage of participants Interval 72.0 to 81.7	71.0 Percentage of participants Interval 65.8 to 76.1	73.9 Percentage of participants Interval 68.6 to 79.1
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 76	77.0 Percentage of participants Interval 72.0 to 82.0	76.0 Percentage of participants Interval 71.1 to 81.0	72.6 Percentage of participants Interval 67.2 to 78.0
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 4	60.0 Percentage of participants Interval 55.1 to 64.8	57.5 Percentage of participants Interval 52.6 to 62.4	53.3 Percentage of participants Interval 48.4 to 58.1
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 8	65.5 Percentage of participants Interval 60.8 to 70.1	66.1 Percentage of participants Interval 61.4 to 70.8	60.0 Percentage of participants Interval 55.1 to 64.9
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 12	69.3 Percentage of participants Interval 64.6 to 74.0	68.8 Percentage of participants Interval 64.1 to 73.6	64.4 Percentage of participants Interval 59.4 to 69.3
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 16	70.6 Percentage of participants Interval 65.8 to 75.3	74.7 Percentage of participants Interval 70.1 to 79.2	66.1 Percentage of participants Interval 61.1 to 71.2
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 20	69.7 Percentage of participants Interval 64.9 to 74.6	70.3 Percentage of participants Interval 65.5 to 75.1	70.3 Percentage of participants Interval 65.4 to 75.3
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 24	76.0 Percentage of participants Interval 71.4 to 80.6	71.0 Percentage of participants Interval 66.3 to 75.8	71.0 Percentage of participants Interval 66.1 to 76.0
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 28	74.5 Percentage of participants Interval 69.9 to 79.1	75.1 Percentage of participants Interval 70.4 to 79.8	71.5 Percentage of participants Interval 66.5 to 76.4
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 32	74.1 Percentage of participants Interval 69.2 to 79.0	74.9 Percentage of participants Interval 70.1 to 79.7	71.4 Percentage of participants Interval 66.3 to 76.5
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 40	75.1 Percentage of participants Interval 70.2 to 80.1	73.6 Percentage of participants Interval 68.5 to 78.7	69.3 Percentage of participants Interval 64.2 to 74.4
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 44	77.7 Percentage of participants Interval 72.9 to 82.5	73.4 Percentage of participants Interval 68.3 to 78.4	70.6 Percentage of participants Interval 65.4 to 75.7
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 48	78.3 Percentage of participants Interval 73.6 to 83.0	72.7 Percentage of participants Interval 67.6 to 77.8	73.4 Percentage of participants Interval 68.4 to 78.4
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 52	76.6 Percentage of participants Interval 71.7 to 81.4	75.2 Percentage of participants Interval 70.2 to 80.2	69.3 Percentage of participants Interval 63.9 to 74.6
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 80	77.5 Percentage of participants Interval 72.5 to 82.4	73.8 Percentage of participants Interval 68.7 to 78.9	74.6 Percentage of participants Interval 69.3 to 79.9
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 88	76.2 Percentage of participants Interval 71.2 to 81.3	73.3 Percentage of participants Interval 68.0 to 78.5	72.2 Percentage of participants Interval 66.7 to 77.7
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 96	74.3 Percentage of participants Interval 69.0 to 79.5	73.4 Percentage of participants Interval 68.3 to 78.5	75.9 Percentage of participants Interval 70.6 to 81.2
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population Week 100	70.3 Percentage of participants Interval 64.9 to 75.7	75.7 Percentage of participants Interval 70.8 to 80.7	75.9 Percentage of participants Interval 70.7 to 81.1

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. At each timepoint, only participants with non-missing, valid assessments were included in the analysis.

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥69 vs. \<69 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 4	60.4 Percentage of participants Interval 55.0 to 65.8	60.4 Percentage of participants Interval 54.9 to 65.9	55.7 Percentage of participants Interval 50.1 to 61.2
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 8	66.5 Percentage of participants Interval 61.3 to 71.6	69.6 Percentage of participants Interval 64.3 to 74.8	62.0 Percentage of participants Interval 56.5 to 67.6
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 12	69.3 Percentage of participants Interval 64.1 to 74.5	70.6 Percentage of participants Interval 65.3 to 75.9	66.2 Percentage of participants Interval 60.5 to 71.8
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 16	68.5 Percentage of participants Interval 63.1 to 74.0	75.8 Percentage of participants Interval 70.8 to 80.9	68.5 Percentage of participants Interval 62.8 to 74.2
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 20	67.8 Percentage of participants Interval 62.2 to 73.4	72.0 Percentage of participants Interval 66.7 to 77.3	72.7 Percentage of participants Interval 67.1 to 78.2
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 24	74.5 Percentage of participants Interval 69.2 to 79.8	72.6 Percentage of participants Interval 67.3 to 77.9	73.7 Percentage of participants Interval 68.2 to 79.3
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 28	73.1 Percentage of participants Interval 67.8 to 78.4	77.0 Percentage of participants Interval 71.8 to 82.2	73.7 Percentage of participants Interval 68.2 to 79.3
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 32	72.4 Percentage of participants Interval 66.7 to 78.1	75.8 Percentage of participants Interval 70.4 to 81.2	71.8 Percentage of participants Interval 65.8 to 77.7
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 36	79.4 Percentage of participants Interval 74.0 to 84.7	73.4 Percentage of participants Interval 67.6 to 79.1	74.7 Percentage of participants Interval 68.9 to 80.5
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 40	74.6 Percentage of participants Interval 68.9 to 80.3	75.8 Percentage of participants Interval 70.2 to 81.4	70.6 Percentage of participants Interval 64.7 to 76.6
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 44	76.9 Percentage of participants Interval 71.3 to 82.4	76.4 Percentage of participants Interval 70.8 to 82.0	71.1 Percentage of participants Interval 65.2 to 77.1
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 48	75.7 Percentage of participants Interval 70.2 to 81.2	75.3 Percentage of participants Interval 69.8 to 80.9	74.3 Percentage of participants Interval 68.6 to 80.0
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 52	74.4 Percentage of participants Interval 68.7 to 80.1	77.5 Percentage of participants Interval 71.9 to 83.0	71.7 Percentage of participants Interval 65.6 to 77.7
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 56	77.9 Percentage of participants Interval 72.4 to 83.4	74.0 Percentage of participants Interval 68.2 to 79.7	76.9 Percentage of participants Interval 71.3 to 82.5
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 60	75.2 Percentage of participants Interval 69.4 to 81.0	78.3 Percentage of participants Interval 72.8 to 83.8	73.4 Percentage of participants Interval 67.5 to 79.3
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 64	75.5 Percentage of participants Interval 69.9 to 81.0	74.4 Percentage of participants Interval 68.9 to 80.0	77.0 Percentage of participants Interval 71.2 to 82.7
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 68	77.9 Percentage of participants Interval 72.4 to 83.3	75.5 Percentage of participants Interval 69.9 to 81.0	77.6 Percentage of participants Interval 71.7 to 83.5
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 72	75.9 Percentage of participants Interval 70.3 to 81.4	74.5 Percentage of participants Interval 68.9 to 80.1	76.7 Percentage of participants Interval 70.7 to 82.6
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 76	75.8 Percentage of participants Interval 70.1 to 81.5	78.0 Percentage of participants Interval 72.6 to 83.3	72.7 Percentage of participants Interval 66.3 to 79.1
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 80	76.8 Percentage of participants Interval 71.2 to 82.5	76.5 Percentage of participants Interval 70.9 to 82.1	76.4 Percentage of participants Interval 70.2 to 82.6
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 84	77.8 Percentage of participants Interval 72.3 to 83.3	77.8 Percentage of participants Interval 72.4 to 83.2	75.7 Percentage of participants Interval 69.5 to 81.9
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 88	75.7 Percentage of participants Interval 69.9 to 81.5	76.0 Percentage of participants Interval 70.1 to 81.9	71.8 Percentage of participants Interval 65.2 to 78.3
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 92	77.7 Percentage of participants Interval 71.9 to 83.4	79.9 Percentage of participants Interval 74.7 to 85.2	75.9 Percentage of participants Interval 69.7 to 82.1
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 96	73.5 Percentage of participants Interval 67.4 to 79.5	75.5 Percentage of participants Interval 69.9 to 81.2	77.3 Percentage of participants Interval 71.1 to 83.4
Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population Week 100	70.8 Percentage of participants Interval 64.6 to 76.9	77.0 Percentage of participants Interval 71.4 to 82.5	77.6 Percentage of participants Interval 71.6 to 83.6

SECONDARY outcome

Timeframe: Baseline, average of Weeks 48, 52, and 56

Population: ITT Population and Treatment-Naive Population. Only participants with at least one non-missing, valid assessment at Weeks 48, 52, or 56 were included in the analysis.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=276 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=276 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=271 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations ITT Population	1.9 Percentage of participants Interval 0.3 to 3.5	1.7 Percentage of participants Interval 0.3 to 3.2	2.3 Percentage of participants Interval 0.5 to 4.1
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations Treatment-Naive Population	1.9 Percentage of participants Interval 0.1 to 3.7	1.8 Percentage of participants Interval 0.1 to 3.5	2.6 Percentage of participants Interval 0.4 to 4.8

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement invisual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 8	3.0 Percentage of participants Interval 1.1 to 4.8	2.0 Percentage of participants Interval 0.4 to 3.5	2.0 Percentage of participants Interval 0.4 to 3.5
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 32	1.2 Percentage of participants Interval 0.0 to 2.4	1.8 Percentage of participants Interval 0.2 to 3.3	1.1 Percentage of participants Interval 0.0 to 2.4
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 20	1.7 Percentage of participants Interval 0.3 to 3.2	1.7 Percentage of participants Interval 0.2 to 3.1	1.3 Percentage of participants Interval 0.0 to 2.7
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 4	2.6 Percentage of participants Interval 0.9 to 4.3	1.6 Percentage of participants Interval 0.2 to 3.0	1.9 Percentage of participants Interval 0.4 to 3.4
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 12	2.0 Percentage of participants Interval 0.5 to 3.5	1.6 Percentage of participants Interval 0.2 to 3.0	1.6 Percentage of participants Interval 0.2 to 3.0
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 16	2.1 Percentage of participants Interval 0.5 to 3.7	1.6 Percentage of participants Interval 0.2 to 3.0	0.7 Percentage of participants Interval 0.0 to 1.6
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 24	1.7 Percentage of participants Interval 0.3 to 3.2	1.7 Percentage of participants Interval 0.3 to 3.1	0.7 Percentage of participants Interval 0.0 to 1.6
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 28	1.4 Percentage of participants Interval 0.1 to 2.8	1.4 Percentage of participants Interval 0.1 to 2.7	1.4 Percentage of participants Interval 0.1 to 2.8
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 36	1.6 Percentage of participants Interval 0.1 to 3.1	1.5 Percentage of participants Interval 0.1 to 3.0	1.6 Percentage of participants Interval 0.1 to 3.1
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 40	2.3 Percentage of participants Interval 0.5 to 4.1	1.5 Percentage of participants Interval 0.1 to 2.9	1.5 Percentage of participants Interval 0.1 to 3.0
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 44	1.9 Percentage of participants Interval 0.3 to 3.6	1.4 Percentage of participants Interval 0.1 to 2.8	3.1 Percentage of participants Interval 1.0 to 5.2
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 48	2.3 Percentage of participants Interval 0.5 to 4.1	1.8 Percentage of participants Interval 0.3 to 3.3	1.6 Percentage of participants Interval 0.1 to 3.1
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 52	1.5 Percentage of participants Interval 0.1 to 3.0	1.5 Percentage of participants Interval 0.1 to 2.9	2.0 Percentage of participants Interval 0.3 to 3.8
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 56	1.6 Percentage of participants Interval 0.1 to 3.1	1.9 Percentage of participants Interval 0.3 to 3.5	1.5 Percentage of participants Interval 0.0 to 3.0
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 60	1.2 Percentage of participants Interval 0.0 to 2.5	1.4 Percentage of participants Interval 0.1 to 2.8	1.9 Percentage of participants Interval 0.3 to 3.5
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 64	2.5 Percentage of participants Interval 0.6 to 4.3	1.8 Percentage of participants Interval 0.2 to 3.3	1.2 Percentage of participants Interval 0.0 to 2.6
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 68	2.4 Percentage of participants Interval 0.6 to 4.3	1.8 Percentage of participants Interval 0.3 to 3.4	1.3 Percentage of participants Interval 0.0 to 2.7
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 72	1.6 Percentage of participants Interval 0.1 to 3.1	1.5 Percentage of participants Interval 0.1 to 2.9	1.3 Percentage of participants Interval 0.0 to 2.7
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 76	1.6 Percentage of participants Interval 0.1 to 3.2	3.4 Percentage of participants Interval 1.3 to 5.6	0.9 Percentage of participants Interval 0.0 to 2.1
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 80	2.0 Percentage of participants Interval 0.3 to 3.8	3.0 Percentage of participants Interval 1.0 to 5.0	0.9 Percentage of participants Interval 0.0 to 2.1
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 84	1.6 Percentage of participants Interval 0.1 to 3.2	1.0 Percentage of participants Interval 0.0 to 2.2	0.9 Percentage of participants Interval 0.0 to 2.1
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 88	1.7 Percentage of participants Interval 0.1 to 3.2	2.0 Percentage of participants Interval 0.3 to 3.8	1.3 Percentage of participants Interval 0.0 to 2.7
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 92	2.1 Percentage of participants Interval 0.4 to 3.9	2.8 Percentage of participants Interval 0.8 to 4.8	2.2 Percentage of participants Interval 0.3 to 4.0
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 96	2.1 Percentage of participants Interval 0.3 to 3.8	0.9 Percentage of participants Interval 0.0 to 2.1	1.7 Percentage of participants Interval 0.1 to 3.4
Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population Week 100	2.1 Percentage of participants Interval 0.3 to 3.8	1.2 Percentage of participants Interval 0.0 to 2.6	2.5 Percentage of participants Interval 0.5 to 4.5

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. At each timepoint, only participants with non-missing, valid assessments were included in the analysis.

Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

SECONDARY outcome

Timeframe: Baseline, Weeks 16, 52, and 96

Population: ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Only participants with non-missing, valid assessments at Baseline and each timepoint were included in the analysis.

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population Week 16	35.0 Percentage of participants Interval 29.6 to 40.5	28.9 Percentage of participants Interval 23.9 to 34.0	36.7 Percentage of participants Interval 31.2 to 42.3
Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population Week 52	42.3 Percentage of participants Interval 36.4 to 48.3	35.4 Percentage of participants Interval 29.6 to 41.2	46.2 Percentage of participants Interval 40.0 to 52.3
Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population Week 96	42.8 Percentage of participants Interval 36.6 to 49.0	42.2 Percentage of participants Interval 35.9 to 48.5	51.4 Percentage of participants Interval 44.8 to 57.9

SECONDARY outcome

Timeframe: Baseline, Weeks 16, 52, and 96

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. Only participants with non-missing, valid assessments at Baseline and each timepoint were included in the analysis.

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population Week 16	39.5 Percentage of participants Interval 33.2 to 45.9	33.3 Percentage of participants Interval 27.1 to 39.4	39.3 Percentage of participants Interval 32.7 to 45.8
Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population Week 52	47.4 Percentage of participants Interval 40.5 to 54.4	42.3 Percentage of participants Interval 35.3 to 49.3	49.5 Percentage of participants Interval 42.3 to 56.8
Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population Week 96	47.0 Percentage of participants Interval 39.7 to 54.2	49.1 Percentage of participants Interval 41.7 to 56.6	52.3 Percentage of participants Interval 44.6 to 60.1

SECONDARY outcome

Timeframe: Baseline, Weeks 16, 52, and 96

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population Week 16	12.8 Percentage of participants Interval 9.0 to 16.6	10.3 Percentage of participants Interval 6.8 to 13.8	12.7 Percentage of participants Interval 8.8 to 16.5
Percentage of Participants With a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population Week 52	15.3 Percentage of participants Interval 10.9 to 19.8	14.2 Percentage of participants Interval 10.0 to 18.5	17.0 Percentage of participants Interval 12.3 to 21.6
Percentage of Participants With a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population Week 96	14.6 Percentage of participants Interval 10.0 to 19.1	20.9 Percentage of participants Interval 15.8 to 26.0	22.4 Percentage of participants Interval 16.9 to 27.8

SECONDARY outcome

Timeframe: Baseline, Weeks 16, 52, and 96

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. Only participants with non-missing, valid assessments at Baseline and each timepoint were included in the analysis.

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population Week 16	15.1 Percentage of participants Interval 10.4 to 19.8	10.4 Percentage of participants Interval 6.4 to 14.4	14.4 Percentage of participants Interval 9.7 to 19.1
Percentage of Participants With a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population Week 52	17.4 Percentage of participants Interval 12.1 to 22.8	16.4 Percentage of participants Interval 11.2 to 21.6	19.5 Percentage of participants Interval 13.7 to 25.2
Percentage of Participants With a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population Week 96	17.1 Percentage of participants Interval 11.5 to 22.6	25.3 Percentage of participants Interval 18.9 to 31.6	23.9 Percentage of participants Interval 17.3 to 30.5

SECONDARY outcome

Timeframe: Baseline, Weeks 16, 52, and 96

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population Week 16	3.5 Percentage of participants Interval 1.4 to 5.6	3.9 Percentage of participants Interval 1.7 to 6.2	3.6 Percentage of participants Interval 1.4 to 5.8
Percentage of Participants With a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population Week 52	4.9 Percentage of participants Interval 2.2 to 7.7	4.5 Percentage of participants Interval 1.9 to 7.0	5.8 Percentage of participants Interval 2.9 to 8.7
Percentage of Participants With a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population Week 96	5.8 Percentage of participants Interval 2.8 to 8.8	6.0 Percentage of participants Interval 3.0 to 9.0	5.9 Percentage of participants Interval 2.8 to 9.0

SECONDARY outcome

Timeframe: Baseline, Weeks 16, 52, and 96

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. Only participants with non-missing, valid assessments at Baseline and each timepoint were included in the analysis.

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population Week 52	5.1 Percentage of participants Interval 2.0 to 8.3	4.2 Percentage of participants Interval 1.4 to 7.0	6.2 Percentage of participants Interval 2.7 to 9.7
Percentage of Participants With a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population Week 16	3.5 Percentage of participants Interval 1.1 to 5.9	3.6 Percentage of participants Interval 1.2 to 6.1	3.9 Percentage of participants Interval 1.3 to 6.4
Percentage of Participants With a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population Week 96	6.8 Percentage of participants Interval 3.1 to 10.5	6.3 Percentage of participants Interval 2.8 to 9.8	7.0 Percentage of participants Interval 3.0 to 11.0

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: ITT Population and Treatment-Naive Population. Only participants with non-missing, valid assessments at Baseline and Week 52 were included in the analysis.

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). PDR was defined as an ETDRS DRSS score of ≥61 on the 7-field/4-wide field color fundus photographs assessment by a central reading center. The weighted percentages of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% CI is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=224 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=214 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=219 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Without Proliferative Diabetic Retinopathy (PDR) at Baseline Who Developed New PDR at Week 52, ITT and Treatment-Naive Populations ITT Population	0.9 Percentage of participants Interval 0.0 to 2.2	0.5 Percentage of participants Interval 0.0 to 1.4	0.9 Percentage of participants Interval 0.0 to 2.2
Percentage of Participants Without Proliferative Diabetic Retinopathy (PDR) at Baseline Who Developed New PDR at Week 52, ITT and Treatment-Naive Populations Treatment-Naive Population	1.2 Percentage of participants Interval 0.0 to 2.8	0.6 Percentage of participants Interval 0.0 to 1.9	0.0 Percentage of participants Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: ITT Population and Treatment-Naive Population. Only participants with non-missing, valid assessments at Baseline and Week 52 were included in the analysis.

The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced PDR. High-risk PDR was defined as an ETDRS DRSS score of ≥71 on the 7-field/4-wide field color fundus photographs assessment by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% CI is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=241 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=227 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=237 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Without High-Risk Proliferative Diabetic Retinopathy (PDR) at Baseline Who Developed High-Risk PDR at Week 52, ITT and Treatment-Naive Populations ITT Population	0.0 Percentage of participants Interval 0.0 to 0.0	0.0 Percentage of participants Interval 0.0 to 0.0	0.4 Percentage of participants Interval 0.0 to 1.2
Percentage of Participants Without High-Risk Proliferative Diabetic Retinopathy (PDR) at Baseline Who Developed High-Risk PDR at Week 52, ITT and Treatment-Naive Populations Treatment-Naive Population	0.0 Percentage of participants Interval 0.0 to 0.0	0.0 Percentage of participants Interval 0.0 to 0.0	0.0 Percentage of participants Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Week 52

Population: ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. The number analyzed includes all participants in Arm B: Faricimab 6 mg PTI who had not discontinued the study prior to Week 52.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=286 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, ITT Population Once Every 4 Weeks	—	—	10.8 Percentage of participants Interval 7.2 to 14.4
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, ITT Population Once Every 8 Weeks	—	—	15.4 Percentage of participants Interval 11.2 to 19.6
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, ITT Population Once Every 12 Weeks	—	—	21.0 Percentage of participants Interval 16.3 to 25.7
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, ITT Population Once Every 16 Weeks	—	—	52.8 Percentage of participants Interval 47.0 to 58.6

SECONDARY outcome

Timeframe: Week 52

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. The number analyzed includes all participants in Arm B: Faricimab 6 mg PTI who had not discontinued the study prior to Week 52.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=222 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, Treatment-Naive Population Once Every 4 Weeks	—	—	9.0 Percentage of participants Interval 5.2 to 12.8
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, Treatment-Naive Population Once Every 8 Weeks	—	—	14.4 Percentage of participants Interval 9.8 to 19.0
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, Treatment-Naive Population Once Every 12 Weeks	—	—	22.1 Percentage of participants Interval 16.6 to 27.5
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, Treatment-Naive Population Once Every 16 Weeks	—	—	54.5 Percentage of participants Interval 47.9 to 61.1

SECONDARY outcome

Timeframe: Week 96

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=270 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, ITT Population Once Every 4 Weeks	—	—	7.0 Percentage of participants Interval 4.0 to 10.1
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, ITT Population Once Every 8 Weeks	—	—	14.8 Percentage of participants Interval 10.6 to 19.1
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, ITT Population Once Every 12 Weeks	—	—	18.1 Percentage of participants Interval 13.5 to 22.8
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, ITT Population Once Every 16 Weeks	—	—	60.0 Percentage of participants Interval 54.1 to 65.9

SECONDARY outcome

Timeframe: Week 96

Population: Treatment-Naive Population: all participants randomized in the study who had not received any intravitreal anti-VEGF agents in the study eye prior to randomization. Participants were grouped according to the treatment assigned at randomization. The number analyzed includes all participants in Arm B: Faricimab 6 mg PTI who had not discontinued the study prior to Week 96.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=208 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, Treatment-Naive Population Once Every 4 Weeks	—	—	7.2 Percentage of participants Interval 3.7 to 10.7
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, Treatment-Naive Population Once Every 8 Weeks	—	—	11.1 Percentage of participants Interval 6.8 to 15.3
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, Treatment-Naive Population Once Every 12 Weeks	—	—	16.8 Percentage of participants Interval 11.7 to 21.9
Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, Treatment-Naive Population Once Every 16 Weeks	—	—	64.9 Percentage of participants Interval 58.4 to 71.4

SECONDARY outcome

Timeframe: From start of PTI (Week 12 or later) until Week 52

Population: ITT Population and Treatment-Naive Population. The number analyzed includes all participants in Arm B: Faricimab 6 mg PTI who had not discontinued the study prior to Week 52.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=286 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants in the Faricimab 6 mg PTI Arm at Week 52 Who Achieved a Once Every 12-Weeks or 16-Weeks Treatment Interval Without an Interval Decrease Below Once Every 12 Weeks, ITT and Treatment-Naive Populations ITT Population	—	—	67.8 Percentage of participants Interval 62.4 to 73.3
Percentage of Participants in the Faricimab 6 mg PTI Arm at Week 52 Who Achieved a Once Every 12-Weeks or 16-Weeks Treatment Interval Without an Interval Decrease Below Once Every 12 Weeks, ITT and Treatment-Naive Populations Treatment-Naive Population	—	—	71.6 Percentage of participants Interval 65.7 to 77.6

SECONDARY outcome

Timeframe: From start of PTI (Week 12 or later) until Week 96

Population: ITT Population and Treatment-Naive Population. The number analyzed includes all participants in Arm B: Faricimab 6 mg PTI who had not discontinued the study prior to Week 96.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=270 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants in the Faricimab 6 mg PTI Arm at Week 96 Who Achieved a Once Every 12-Weeks or 16-Weeks Treatment Interval Without an Interval Decrease Below Once Every 12 Weeks, ITT and Treatment-Naive Populations ITT Population	—	—	60.4 Percentage of participants Interval 54.5 to 66.2
Percentage of Participants in the Faricimab 6 mg PTI Arm at Week 96 Who Achieved a Once Every 12-Weeks or 16-Weeks Treatment Interval Without an Interval Decrease Below Once Every 12 Weeks, ITT and Treatment-Naive Populations Treatment-Naive Population	—	—	64.4 Percentage of participants Interval 57.9 to 70.9

SECONDARY outcome

Timeframe: From Baseline through Week 56

Population: ITT Population and Treatment-Naive Population

Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline CST (continuous), baseline BCVA (\<64 vs. ≥64 letters), prior intravitreal anti-VEGF therapy (yes vs. no), and region of enrollment (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Change From Baseline in Central Subfield Thickness in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations ITT Population	-196.5 microns Interval -204.7 to -188.4	-170.3 microns Interval -178.5 to -162.2	-206.6 microns Interval -214.7 to -198.4
Change From Baseline in Central Subfield Thickness in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations Treatment-Naive Population	-197.5 microns Interval -206.2 to -188.8	-173.6 microns Interval -182.3 to -164.8	-204.6 microns Interval -213.5 to -195.7

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Population: ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 32	-181.6 microns Interval -190.8 to -172.4	-147.2 microns Interval -156.4 to -138.0	-200.2 microns Interval -209.4 to -191.0
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 84	-204.9 microns Interval -214.1 to -195.7	-186.2 microns Interval -195.5 to -176.9	-211.8 microns Interval -221.1 to -202.5
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 4	-124.9 microns Interval -135.0 to -114.8	-111.0 microns Interval -121.2 to -100.8	-118.4 microns Interval -128.5 to -108.2
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 8	-149.6 microns Interval -159.0 to -140.3	-130.9 microns Interval -140.4 to -121.5	-145.9 microns Interval -155.2 to -136.5
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 12	-168.4 microns Interval -177.1 to -159.8	-144.7 microns Interval -153.4 to -136.0	-165.6 microns Interval -174.3 to -156.9
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 16	-182.1 microns Interval -190.4 to -173.7	-152.7 microns Interval -161.1 to -144.3	-177.6 microns Interval -186.0 to -169.2
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 20	-174.6 microns Interval -183.1 to -166.0	-159.0 microns Interval -167.6 to -150.4	-184.6 microns Interval -193.2 to -176.1
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 24	-192.8 microns Interval -201.2 to -184.3	-146.3 microns Interval -154.7 to -137.8	-196.4 microns Interval -204.8 to -188.0
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 28	-193.7 microns Interval -203.4 to -184.0	-163.8 microns Interval -173.6 to -154.0	-174.6 microns Interval -184.4 to -164.9
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 36	-201.0 microns Interval -210.6 to -191.5	-166.0 microns Interval -175.7 to -156.4	-179.4 microns Interval -188.9 to -169.8
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 40	-193.5 microns Interval -203.0 to -184.1	-153.9 microns Interval -163.4 to -144.4	-205.1 microns Interval -214.5 to -195.7
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 44	-189.2 microns Interval -199.1 to -179.3	-172.6 microns Interval -182.6 to -162.6	-187.5 microns Interval -197.4 to -177.5
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 48	-194.8 microns Interval -203.7 to -185.8	-163.2 microns Interval -172.2 to -154.3	-209.7 microns Interval -218.6 to -200.8
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 52	-193.0 microns Interval -202.6 to -183.4	-179.2 microns Interval -188.9 to -169.5	-191.0 microns Interval -200.6 to -181.4
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 56	-200.3 microns Interval -209.3 to -191.2	-164.4 microns Interval -173.5 to -155.2	-212.4 microns Interval -221.5 to -203.4
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 60	-196.3 microns Interval -205.9 to -186.6	-182.0 microns Interval -191.7 to -172.3	-197.8 microns Interval -207.4 to -188.2
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 64	-199.9 microns Interval -208.9 to -190.8	-171.5 microns Interval -180.6 to -162.4	-214.9 microns Interval -224.0 to -205.9
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 68	-200.9 microns Interval -209.7 to -192.1	-186.8 microns Interval -195.7 to -177.9	-201.1 microns Interval -210.0 to -192.3
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 72	-201.6 microns Interval -210.3 to -193.0	-182.3 microns Interval -191.1 to -173.6	-216.2 microns Interval -224.9 to -207.6
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 76	-200.7 microns Interval -209.8 to -191.7	-188.4 microns Interval -197.6 to -179.3	-206.0 microns Interval -215.1 to -197.0
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 80	-203.2 microns Interval -211.7 to -194.6	-184.5 microns Interval -193.2 to -175.9	-219.1 microns Interval -227.7 to -210.5
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 88	-204.1 microns Interval -213.4 to -194.8	-183.7 microns Interval -193.1 to -174.3	-218.6 microns Interval -228.0 to -209.3
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 92	-202.4 microns Interval -211.4 to -193.3	-193.9 microns Interval -203.2 to -184.7	-210.9 microns Interval -220.1 to -201.7
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 96	-203.8 microns Interval -212.6 to -195.1	-194.7 microns Interval -203.6 to -185.8	-224.0 microns Interval -232.9 to -215.1
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population Week 100	-207.3 microns Interval -216.0 to -198.6	-200.2 microns Interval -209.0 to -191.4	-213.1 microns Interval -221.8 to -204.3

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline CST (continuous), baseline BCVA (\<64 vs. ≥64 letters), and region of enrollment (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=245 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=242 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=238 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 28	-194.0 microns Interval -204.4 to -183.5	-167.5 microns Interval -178.0 to -156.9	-177.4 microns Interval -188.1 to -166.7
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 56	-200.9 microns Interval -210.3 to -191.5	-171.0 microns Interval -180.6 to -161.4	-210.4 microns Interval -220.0 to -200.8
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 68	-201.7 microns Interval -211.2 to -192.1	-189.1 microns Interval -198.8 to -179.5	-201.5 microns Interval -211.2 to -191.7
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 76	-202.1 microns Interval -211.8 to -192.4	-189.8 microns Interval -199.7 to -180.0	-204.8 microns Interval -214.8 to -194.9
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 80	-202.2 microns Interval -211.6 to -192.7	-186.2 microns Interval -195.9 to -176.6	-217.3 microns Interval -227.0 to -207.5
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 4	-121.5 microns Interval -132.1 to -110.9	-110.1 microns Interval -120.9 to -99.3	-116.1 microns Interval -127.0 to -105.2
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 8	-147.4 microns Interval -157.3 to -137.5	-131.5 microns Interval -141.5 to -121.5	-142.9 microns Interval -153.0 to -132.8
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 12	-166.7 microns Interval -175.7 to -157.8	-147.4 microns Interval -156.4 to -138.3	-162.8 microns Interval -171.9 to -153.6
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 16	-181.7 microns Interval -190.3 to -173.1	-155.9 microns Interval -164.5 to -147.2	-175.1 microns Interval -183.8 to -166.3
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 20	-178.1 microns Interval -187.0 to -169.2	-161.6 microns Interval -170.6 to -152.6	-182.9 microns Interval -192.0 to -173.8
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 24	-191.1 microns Interval -200.2 to -182.0	-149.7 microns Interval -158.9 to -140.6	-194.2 microns Interval -203.4 to -184.9
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 32	-183.7 microns Interval -193.7 to -173.8	-150.2 microns Interval -160.3 to -140.2	-196.4 microns Interval -206.6 to -186.2
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 36	-203.6 microns Interval -213.3 to -193.8	-168.7 microns Interval -178.6 to -158.9	-181.9 microns Interval -191.9 to -171.9
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 40	-192.1 microns Interval -202.8 to -181.4	-157.4 microns Interval -168.2 to -146.5	-198.9 microns Interval -209.7 to -188.1
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 44	-189.3 microns Interval -200.2 to -178.3	-172.9 microns Interval -184.0 to -161.8	-187.3 microns Interval -198.5 to -176.1
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 48	-194.9 microns Interval -204.7 to -185.1	-165.0 microns Interval -174.9 to -155.1	-207.3 microns Interval -217.3 to -197.3
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 52	-196.2 microns Interval -206.5 to -185.9	-181.1 microns Interval -191.6 to -170.5	-191.1 microns Interval -201.7 to -180.5
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 60	-198.0 microns Interval -208.4 to -187.5	-185.1 microns Interval -195.6 to -174.5	-195.0 microns Interval -205.6 to -184.4
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 64	-199.2 microns Interval -208.8 to -189.6	-175.3 microns Interval -184.9 to -165.6	-213.7 microns Interval -223.5 to -203.9
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 72	-203.2 microns Interval -212.5 to -193.9	-184.1 microns Interval -193.5 to -174.6	-215.9 microns Interval -225.5 to -206.4
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 84	-202.9 microns Interval -213.2 to -192.7	-185.7 microns Interval -196.1 to -175.2	-211.0 microns Interval -221.6 to -200.4
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 88	-205.2 microns Interval -215.3 to -195.0	-186.4 microns Interval -196.7 to -176.1	-215.9 microns Interval -226.4 to -205.5
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 92	-202.2 microns Interval -212.0 to -192.5	-195.9 microns Interval -205.9 to -186.0	-208.8 microns Interval -218.9 to -198.7
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 96	-199.0 microns Interval -209.0 to -189.1	-196.7 microns Interval -206.9 to -186.6	-221.0 microns Interval -231.4 to -210.7
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population Week 100	-206.7 microns Interval -215.7 to -197.7	-201.3 microns Interval -210.5 to -192.1	-213.4 microns Interval -222.7 to -204.1

SECONDARY outcome

Timeframe: Average of Weeks 48, 52, and 56

Population: ITT Population and Treatment-Naive Population. Only participants with at least one non-missing, valid assessment at Weeks 48, 52, or 56 were included in the analysis.

Absence of diabetic macular edema was defined as achieving a central subfield thickness (CST) of \<325 microns in the study eye. CST was defined as the distance between the internal limiting membrane and Bruch's membrane. For each participant, an average CST value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=276 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=275 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=272 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations Treatment-Naive Population	80.4 Percentage of participants Interval 75.1 to 85.7	68.3 Percentage of participants Interval 62.1 to 74.4	83.5 Percentage of participants Interval 78.4 to 88.5
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations ITT Population	78.0 Percentage of participants Interval 73.1 to 82.8	65.4 Percentage of participants Interval 59.9 to 70.8	81.3 Percentage of participants Interval 76.8 to 85.9

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Absence of diabetic macular edema was defined as achieving a central subfield thickness of \<325 microns in the study eye. Central subfield thickness was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 8	52.7 Percentage of participants Interval 47.2 to 58.2	42.6 Percentage of participants Interval 37.1 to 48.2	48.4 Percentage of participants Interval 42.9 to 54.0
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 20	70.7 Percentage of participants Interval 65.6 to 75.8	58.9 Percentage of participants Interval 53.4 to 64.5	71.1 Percentage of participants Interval 65.9 to 76.2
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 32	72.1 Percentage of participants Interval 66.8 to 77.4	55.8 Percentage of participants Interval 50.1 to 61.5	79.0 Percentage of participants Interval 74.2 to 83.8
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 40	80.8 Percentage of participants Interval 76.1 to 85.5	58.8 Percentage of participants Interval 53.0 to 64.7	82.3 Percentage of participants Interval 77.9 to 86.7
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 64	80.0 Percentage of participants Interval 75.2 to 84.8	67.7 Percentage of participants Interval 62.1 to 73.3	88.3 Percentage of participants Interval 84.4 to 92.2
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 68	84.1 Percentage of participants Interval 79.7 to 88.5	74.8 Percentage of participants Interval 69.4 to 80.1	83.5 Percentage of participants Interval 79.0 to 88.1
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 72	85.2 Percentage of participants Interval 81.0 to 89.5	70.2 Percentage of participants Interval 64.5 to 75.9	88.0 Percentage of participants Interval 84.0 to 92.0
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 76	84.9 Percentage of participants Interval 80.5 to 89.2	76.0 Percentage of participants Interval 70.7 to 81.2	85.6 Percentage of participants Interval 81.3 to 89.8
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 80	81.9 Percentage of participants Interval 77.3 to 86.6	73.2 Percentage of participants Interval 67.7 to 78.7	88.5 Percentage of participants Interval 84.5 to 92.4
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 84	86.1 Percentage of participants Interval 82.0 to 90.3	74.9 Percentage of participants Interval 69.5 to 80.3	85.1 Percentage of participants Interval 80.7 to 89.5
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 88	83.2 Percentage of participants Interval 78.7 to 87.7	74.2 Percentage of participants Interval 68.7 to 79.6	90.4 Percentage of participants Interval 86.8 to 94.0
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 92	78.2 Percentage of participants Interval 73.2 to 83.3	78.2 Percentage of participants Interval 73.1 to 83.3	86.5 Percentage of participants Interval 82.3 to 90.7
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 96	83.7 Percentage of participants Interval 79.2 to 88.2	77.3 Percentage of participants Interval 72.1 to 82.4	91.8 Percentage of participants Interval 88.4 to 95.3
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 100	85.9 Percentage of participants Interval 81.7 to 90.1	81.0 Percentage of participants Interval 76.1 to 86.0	89.5 Percentage of participants Interval 85.7 to 93.4
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 4	41.3 Percentage of participants Interval 35.9 to 46.8	35.0 Percentage of participants Interval 29.7 to 40.4	36.1 Percentage of participants Interval 30.8 to 41.4
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 12	67.4 Percentage of participants Interval 62.1 to 72.6	49.6 Percentage of participants Interval 44.0 to 55.2	60.9 Percentage of participants Interval 55.4 to 66.4
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 16	72.0 Percentage of participants Interval 66.9 to 77.0	58.6 Percentage of participants Interval 53.1 to 64.1	67.2 Percentage of participants Interval 61.8 to 72.5
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 24	81.3 Percentage of participants Interval 76.8 to 85.8	53.7 Percentage of participants Interval 48.1 to 59.4	76.5 Percentage of participants Interval 71.7 to 81.4
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 28	79.3 Percentage of participants Interval 74.6 to 84.0	62.5 Percentage of participants Interval 57.0 to 68.0	71.4 Percentage of participants Interval 66.2 to 76.5
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 36	81.7 Percentage of participants Interval 77.1 to 86.3	63.1 Percentage of participants Interval 57.4 to 68.8	70.9 Percentage of participants Interval 65.6 to 76.1
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 44	79.0 Percentage of participants Interval 74.3 to 83.8	67.6 Percentage of participants Interval 62.1 to 73.1	74.7 Percentage of participants Interval 69.6 to 79.9
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 48	81.5 Percentage of participants Interval 76.8 to 86.1	64.0 Percentage of participants Interval 58.3 to 69.7	86.5 Percentage of participants Interval 82.5 to 90.5
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 52	78.3 Percentage of participants Interval 73.4 to 83.1	71.1 Percentage of participants Interval 65.6 to 76.7	77.4 Percentage of participants Interval 72.4 to 82.4
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 56	81.3 Percentage of participants Interval 76.6 to 86.0	65.0 Percentage of participants Interval 59.2 to 70.8	86.5 Percentage of participants Interval 82.4 to 90.7
Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population Week 60	79.4 Percentage of participants Interval 74.6 to 84.3	72.3 Percentage of participants Interval 66.9 to 77.7	78.8 Percentage of participants Interval 74.0 to 83.6

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

Retinal dryness was defined as achieving a central subfield thickness (ILM-BM) of \<280 microns. Central subfield thickness was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. The weighted estimates of the percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 4	16.0 Percentage of participants Interval 12.0 to 19.9	12.6 Percentage of participants Interval 8.9 to 16.3	15.4 Percentage of participants Interval 11.5 to 19.4
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 8	24.6 Percentage of participants Interval 19.9 to 29.3	16.2 Percentage of participants Interval 12.1 to 20.3	24.2 Percentage of participants Interval 19.6 to 28.8
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 12	34.1 Percentage of participants Interval 28.9 to 39.4	22.1 Percentage of participants Interval 17.4 to 26.7	32.4 Percentage of participants Interval 27.3 to 37.5
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 16	42.5 Percentage of participants Interval 36.9 to 48.0	23.2 Percentage of participants Interval 18.5 to 27.9	38.4 Percentage of participants Interval 33.0 to 43.9
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 20	40.6 Percentage of participants Interval 35.0 to 46.1	29.7 Percentage of participants Interval 24.5 to 34.8	45.9 Percentage of participants Interval 40.3 to 51.5
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 24	48.1 Percentage of participants Interval 42.4 to 53.8	26.6 Percentage of participants Interval 21.6 to 31.6	53.0 Percentage of participants Interval 47.3 to 58.7
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 28	50.2 Percentage of participants Interval 44.4 to 55.9	34.3 Percentage of participants Interval 28.8 to 39.8	45.9 Percentage of participants Interval 40.1 to 51.7
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 32	43.2 Percentage of participants Interval 37.3 to 49.0	30.6 Percentage of participants Interval 25.1 to 36.1	55.0 Percentage of participants Interval 49.1 to 60.8
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 36	54.3 Percentage of participants Interval 48.4 to 60.3	39.2 Percentage of participants Interval 33.4 to 45.1	48.5 Percentage of participants Interval 42.5 to 54.5
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 40	51.3 Percentage of participants Interval 45.3 to 57.3	32.2 Percentage of participants Interval 26.7 to 37.7	57.5 Percentage of participants Interval 51.8 to 63.2
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 44	51.9 Percentage of participants Interval 46.1 to 57.8	37.1 Percentage of participants Interval 31.4 to 42.8	51.5 Percentage of participants Interval 45.7 to 57.4
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 48	50.1 Percentage of participants Interval 44.2 to 56.0	36.2 Percentage of participants Interval 30.4 to 42.0	63.2 Percentage of participants Interval 57.4 to 69.0
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 52	54.7 Percentage of participants Interval 48.7 to 60.6	42.3 Percentage of participants Interval 36.2 to 48.4	57.8 Percentage of participants Interval 51.9 to 63.7
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 56	56.9 Percentage of participants Interval 51.0 to 62.9	41.2 Percentage of participants Interval 35.1 to 47.2	66.3 Percentage of participants Interval 60.6 to 72.0
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 60	54.0 Percentage of participants Interval 48.0 to 60.0	47.7 Percentage of participants Interval 41.6 to 53.7	60.2 Percentage of participants Interval 54.4 to 66.0
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 64	55.4 Percentage of participants Interval 49.4 to 61.3	47.4 Percentage of participants Interval 41.3 to 53.4	68.5 Percentage of participants Interval 62.8 to 74.1
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 68	57.7 Percentage of participants Interval 51.7 to 63.8	52.3 Percentage of participants Interval 46.1 to 58.5	61.3 Percentage of participants Interval 55.3 to 67.3
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 72	58.5 Percentage of participants Interval 52.6 to 64.3	47.7 Percentage of participants Interval 41.4 to 53.9	65.8 Percentage of participants Interval 60.1 to 71.5
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 76	54.8 Percentage of participants Interval 48.6 to 60.9	53.9 Percentage of participants Interval 47.7 to 60.1	65.9 Percentage of participants Interval 60.1 to 71.8
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 80	54.7 Percentage of participants Interval 48.7 to 60.6	51.1 Percentage of participants Interval 44.8 to 57.3	70.1 Percentage of participants Interval 64.5 to 75.8
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 84	61.2 Percentage of participants Interval 55.5 to 67.0	56.0 Percentage of participants Interval 49.9 to 62.2	67.1 Percentage of participants Interval 61.3 to 72.9
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 88	58.0 Percentage of participants Interval 52.1 to 64.0	54.2 Percentage of participants Interval 48.0 to 60.5	72.2 Percentage of participants Interval 66.7 to 77.7
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 92	58.0 Percentage of participants Interval 52.2 to 63.8	57.9 Percentage of participants Interval 51.7 to 64.0	66.2 Percentage of participants Interval 60.5 to 72.0
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 96	61.4 Percentage of participants Interval 55.6 to 67.2	58.0 Percentage of participants Interval 51.8 to 64.2	72.7 Percentage of participants Interval 67.2 to 78.2
Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population Week 100	60.5 Percentage of participants Interval 54.5 to 66.4	60.7 Percentage of participants Interval 54.5 to 66.8	71.4 Percentage of participants Interval 65.9 to 76.8

SECONDARY outcome

Timeframe: Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100

Intraretinal fluid was measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world); Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time, ITT Population Week 96	47.6 Percentage of participants Interval 41.5 to 53.7	34.6 Percentage of participants Interval 28.7 to 40.6	63.1 Percentage of participants Interval 57.0 to 69.2
Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time, ITT Population Week 100	44.5 Percentage of participants Interval 38.4 to 50.7	37.6 Percentage of participants Interval 31.5 to 43.6	61.4 Percentage of participants Interval 55.2 to 67.5
Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time, ITT Population Week 56	42.7 Percentage of participants Interval 36.7 to 48.7	23.7 Percentage of participants Interval 18.5 to 28.9	49.3 Percentage of participants Interval 43.3 to 55.3
Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time, ITT Population Week 92	43.2 Percentage of participants Interval 37.1 to 49.3	33.2 Percentage of participants Interval 27.4 to 39.1	58.5 Percentage of participants Interval 52.3 to 64.7
Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time, ITT Population Week 16	21.9 Percentage of participants Interval 17.1 to 26.6	13.4 Percentage of participants Interval 9.6 to 17.3	16.3 Percentage of participants Interval 12.0 to 20.5
Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time, ITT Population Week 48	33.2 Percentage of participants Interval 27.5 to 38.9	21.9 Percentage of participants Interval 17.0 to 26.9	45.6 Percentage of participants Interval 39.7 to 51.6
Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time, ITT Population Week 52	38.8 Percentage of participants Interval 32.9 to 44.7	25.5 Percentage of participants Interval 20.2 to 30.8	42.1 Percentage of participants Interval 36.3 to 47.9

SECONDARY outcome

Timeframe: Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100

Subretinal fluid was measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world); Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time, ITT Population Week 16	94.5 Percentage of participants Interval 92.0 to 97.1	95.9 Percentage of participants Interval 93.7 to 98.2	95.3 Percentage of participants Interval 92.9 to 97.7
Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time, ITT Population Week 48	95.5 Percentage of participants Interval 93.1 to 97.9	96.2 Percentage of participants Interval 93.8 to 98.5	97.0 Percentage of participants Interval 95.0 to 99.0
Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time, ITT Population Week 56	97.0 Percentage of participants Interval 95.0 to 99.0	97.3 Percentage of participants Interval 95.3 to 99.3	97.0 Percentage of participants Interval 95.0 to 99.0
Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time, ITT Population Week 100	97.3 Percentage of participants Interval 95.4 to 99.2	97.1 Percentage of participants Interval 95.0 to 99.2	94.3 Percentage of participants Interval 91.4 to 97.2
Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time, ITT Population Week 52	95.4 Percentage of participants Interval 92.9 to 97.9	98.0 Percentage of participants Interval 96.2 to 99.7	95.8 Percentage of participants Interval 93.3 to 98.2
Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time, ITT Population Week 92	94.5 Percentage of participants Interval 91.7 to 97.3	96.7 Percentage of participants Interval 94.5 to 99.0	94.8 Percentage of participants Interval 92.1 to 97.6
Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time, ITT Population Week 96	94.1 Percentage of participants Interval 91.3 to 97.0	96.7 Percentage of participants Interval 94.5 to 98.9	97.0 Percentage of participants Interval 94.8 to 99.1

SECONDARY outcome

Timeframe: Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100

Intraretinal fluid and subretinal fluid were measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. \<64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world); Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time, ITT Population Week 16	21.9 Percentage of participants Interval 17.1 to 26.6	13.1 Percentage of participants Interval 9.3 to 16.9	15.9 Percentage of participants Interval 11.7 to 20.1
Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time, ITT Population Week 48	32.4 Percentage of participants Interval 26.8 to 38.1	21.9 Percentage of participants Interval 17.0 to 26.9	45.2 Percentage of participants Interval 39.3 to 51.2
Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time, ITT Population Week 56	42.4 Percentage of participants Interval 36.4 to 48.3	23.7 Percentage of participants Interval 18.5 to 28.9	47.0 Percentage of participants Interval 41.0 to 53.0
Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time, ITT Population Week 52	38.0 Percentage of participants Interval 32.2 to 43.8	25.5 Percentage of participants Interval 20.2 to 30.8	42.1 Percentage of participants Interval 36.3 to 47.9
Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time, ITT Population Week 92	41.3 Percentage of participants Interval 35.2 to 47.3	32.0 Percentage of participants Interval 26.3 to 37.8	57.2 Percentage of participants Interval 51.0 to 63.4
Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time, ITT Population Week 96	46.0 Percentage of participants Interval 39.8 to 52.1	34.2 Percentage of participants Interval 28.3 to 40.1	62.4 Percentage of participants Interval 56.2 to 68.5
Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time, ITT Population Week 100	43.8 Percentage of participants Interval 37.6 to 49.9	37.4 Percentage of participants Interval 31.4 to 43.5	59.3 Percentage of participants Interval 53.0 to 65.5

SECONDARY outcome

Timeframe: Baseline, Weeks 24, 52, and 100

Population: ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization.

The NEI VFQ-25 captures a patient's perception of vision-related functioning and quality of life. The core measure includes 25 items that comprise 11 vision-related subscales and one item on general health. The composite score ranges from 0 to 100, with higher scores, or a positive change from baseline, indicating better vision-related functioning. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline NEI VFQ-25 Composite Score (continuous), baseline BCVA (\<64 vs. ≥64 letters), prior intravitreal anti-VEGF therapy (yes vs. no), and region of enrollment. An unstructured covariance structure was used. Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% CI is a rounding of 95.04% CI.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=312 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=315 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) Composite Score Over Time, ITT Population Week 52	7.9 score on a scale Interval 6.6 to 9.3	7.5 score on a scale Interval 6.1 to 8.9	7.3 score on a scale Interval 5.9 to 8.6
Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) Composite Score Over Time, ITT Population Week 24	6.9 score on a scale Interval 5.7 to 8.1	6.0 score on a scale Interval 4.8 to 7.2	6.0 score on a scale Interval 4.8 to 7.2
Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) Composite Score Over Time, ITT Population Week 100	7.4 score on a scale Interval 6.0 to 8.8	7.6 score on a scale Interval 6.1 to 9.0	8.0 score on a scale Interval 6.6 to 9.4

SECONDARY outcome

Timeframe: From first dose of study drug through end of study (up to 2 years)

Population: The safety-evaluable population comprised all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye.

This analysis of adverse events (AEs) includes both ocular and non-ocular (systemic) AEs. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. AEs of special interest included the following: Cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law; Suspected transmission of an infectious agent by the study drug; Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, require surgical or medical intervention to prevent permanent loss of sight, or are associated with severe intraocular inflammation.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=311 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=313 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With at Least One Adverse Event Adverse Event (AE)	91.4 Percentage of participants	89.1 Percentage of participants	92.7 Percentage of participants
Percentage of Participants With at Least One Adverse Event Serious AE (SAE)	37.4 Percentage of participants	29.9 Percentage of participants	35.5 Percentage of participants
Percentage of Participants With at Least One Adverse Event AE Leading to Withdrawal from Study Treatment	2.9 Percentage of participants	1.6 Percentage of participants	2.6 Percentage of participants
Percentage of Participants With at Least One Adverse Event AE of Special Interest (AESI)	7.0 Percentage of participants	4.8 Percentage of participants	6.1 Percentage of participants

SECONDARY outcome

Timeframe: From first dose of study drug through end of study (up to 2 years)

Population: The safety-evaluable population comprised all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye.

This analysis of adverse events (AEs) only includes ocular AEs, which are categorized as having occurred either in the study eye or the fellow eye. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. Ocular AEs of special interest included the following: Suspected transmission of an infectious agent by the study drug; Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, require surgical or medical intervention to prevent permanent loss of sight, or are associated with severe intraocular inflammation.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=311 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=313 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Study Eye: Adverse Event (AE)	46.6 Percentage of participants	46.3 Percentage of participants	47.0 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Study Eye: AE Leading to Withdrawal from Treatment	1.9 Percentage of participants	0.3 Percentage of participants	1.3 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Study Eye: Treatment-related AE	2.2 Percentage of participants	1.9 Percentage of participants	3.2 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Study Eye: AESI, Drop in VA Score ≥30 Letters	2.2 Percentage of participants	2.3 Percentage of participants	2.6 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Fellow Eye: AESI, Drop in VA Score ≥30 Letters	1.9 Percentage of participants	1.3 Percentage of participants	2.2 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Fellow Eye: AESI, Intervention Req. to Prevent Permanent Vision Loss	1.3 Percentage of participants	1.0 Percentage of participants	1.0 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Study Eye: Serious AE (SAE)	4.5 Percentage of participants	2.3 Percentage of participants	3.8 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Study Eye: Treatment-related SAE	1.3 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Study Eye: AE of Special Interest (AESI)	4.2 Percentage of participants	2.6 Percentage of participants	3.5 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Study Eye: AESI, Associated with Severe IOI	1.6 Percentage of participants	0.0 Percentage of participants	0.6 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Study Eye: AESI, Intervention Req. to Prevent Permanent Vision Loss	1.3 Percentage of participants	0.3 Percentage of participants	1.0 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Fellow Eye: AE	42.2 Percentage of participants	46.3 Percentage of participants	40.3 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Fellow Eye: SAE	3.5 Percentage of participants	2.3 Percentage of participants	2.9 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Fellow Eye: AESI	2.9 Percentage of participants	2.3 Percentage of participants	2.9 Percentage of participants
Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye Fellow Eye: AESI, Associated with Severe IOI	0.3 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: From first dose of study drug through end of study (up to 2 years)

Population: The safety-evaluable population comprised all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye.

This analysis of adverse events (AEs) only includes non-ocular (systemic) AEs. Investigators sought information on adverse events (AEs) at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. The non-ocular AE of special interest was: Cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=313 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=311 Participants Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=313 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants With at Least One Non-Ocular Adverse Event Adverse Event (AE)	80.2 Percentage of participants	77.8 Percentage of participants	76.7 Percentage of participants
Percentage of Participants With at Least One Non-Ocular Adverse Event Serious AE (SAE)	31.0 Percentage of participants	27.0 Percentage of participants	31.6 Percentage of participants
Percentage of Participants With at Least One Non-Ocular Adverse Event AE Leading to Withdrawal from Study Treatment	1.0 Percentage of participants	1.3 Percentage of participants	1.3 Percentage of participants
Percentage of Participants With at Least One Non-Ocular Adverse Event AE of Special Interest (AESI)	0.0 Percentage of participants	0.3 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With at Least One Non-Ocular Adverse Event AESI, Elevated ALT or AST with Either Elevated Bilirubin or Clinical Jaundice	0.0 Percentage of participants	0.3 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: Pre-dose on Day 1 (Baseline); Weeks 4, 28, 52, 76, and 100

Population: This analysis only included participants in Arms A and B who received treatment with faricimab and with at least one plasma sample, provided sufficient dosing information (dose and dosing time) was available. The number of participants analyzed at a given timepoint includes those with an available plasma sample and dosing information at that timepoint.

Faricimab concentration in plasma was determined using a validated immunoassay method.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=311 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=313 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Plasma Concentration of Faricimab Over Time Week 4	0.0181 micrograms per millilitre (μg/mL) Standard Deviation 0.0139	—	0.0211 micrograms per millilitre (μg/mL) Standard Deviation 0.0337
Plasma Concentration of Faricimab Over Time Baseline	0.0000 micrograms per millilitre (μg/mL) Standard Deviation 0.0001	—	0.0000 micrograms per millilitre (μg/mL) Standard Deviation 0.0001
Plasma Concentration of Faricimab Over Time Week 28	0.0089 micrograms per millilitre (μg/mL) Standard Deviation 0.0145	—	0.0033 micrograms per millilitre (μg/mL) Standard Deviation 0.0053
Plasma Concentration of Faricimab Over Time Week 52	0.0100 micrograms per millilitre (μg/mL) Standard Deviation 0.0132	—	0.0052 micrograms per millilitre (μg/mL) Standard Deviation 0.0104
Plasma Concentration of Faricimab Over Time Week 76	0.0068 micrograms per millilitre (μg/mL) Standard Deviation 0.0255	—	0.0048 micrograms per millilitre (μg/mL) Standard Deviation 0.0085
Plasma Concentration of Faricimab Over Time Week 100	0.0077 micrograms per millilitre (μg/mL) Standard Deviation 0.0126	—	0.0052 micrograms per millilitre (μg/mL) Standard Deviation 0.0087

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 28, 52, 76, and 100

Population: The analysis population consisted of all participants receiving faricimab with at least one determinant post-baseline ADA assessment.

Anti-drug antibodies (ADAs) against fariciamb were detected in plasma using a validated bridging enzyme-linked immunosorbent assay (ELISA). The percentage of participants with treatment-emergent ADA-positive samples includes post-baseline evaluable participants with at least one treatment-induced (defined as having an ADA-negative sample or missing sample at baseline and any positive post-baseline sample) or treatment-boosted (defined as having an ADA-positive sample at baseline and any positive post-baseline sample with a titer that is equal to or greater than 4-fold baseline titer) ADA-positive sample during the study treatment period.

Outcome measures

Outcome measures
Measure	B: Faricimab 6 mg PTI n=311 Participants Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.	A: Faricimab 6 mg Q8W n=310 Participants Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Percentage of Participants Who Test Positive for Treatment-Emergent Anti-Drug Antibodies Against Faricimab During the Study Treatment-Boosted ADA-Positive	0.3 Percentage of participants	—	0.0 Percentage of participants
Percentage of Participants Who Test Positive for Treatment-Emergent Anti-Drug Antibodies Against Faricimab During the Study Treatment-Induced ADA-Positive	10.3 Percentage of participants	—	12.6 Percentage of participants
Percentage of Participants Who Test Positive for Treatment-Emergent Anti-Drug Antibodies Against Faricimab During the Study Total Treatment-Emergent ADA-Positive	10.6 Percentage of participants	—	12.6 Percentage of participants

Adverse Events

A: Faricimab 6 mg Q8W

Serious events: 111 serious events

Other events: 161 other events

Deaths: 16 deaths

B: Faricimab 6 mg PTI

Serious events: 117 serious events

Other events: 163 other events

Deaths: 21 deaths

C: Aflibercept 2 mg Q8W

Serious events: 93 serious events

Other events: 163 other events

Deaths: 13 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	A: Faricimab 6 mg Q8W n=313 participants at risk Participants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.	B: Faricimab 6 mg PTI n=313 participants at risk Participants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.	C: Aflibercept 2 mg Q8W n=311 participants at risk Participants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Eye disorders Cataract	18.5% 58/313 • Number of events 84 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	15.0% 47/313 • Number of events 65 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	17.7% 55/311 • Number of events 82 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Eye disorders Conjunctival haemorrhage	8.0% 25/313 • Number of events 35 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	10.5% 33/313 • Number of events 41 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	7.7% 24/311 • Number of events 32 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Eye disorders Diabetic retinal oedema	6.4% 20/313 • Number of events 27 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	9.3% 29/313 • Number of events 37 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	10.6% 33/311 • Number of events 40 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Eye disorders Vitreous detachment	6.4% 20/313 • Number of events 25 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	7.3% 23/313 • Number of events 28 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	4.2% 13/311 • Number of events 16 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Infections and infestations Nasopharyngitis	8.6% 27/313 • Number of events 31 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	5.8% 18/313 • Number of events 23 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	9.6% 30/311 • Number of events 39 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Vascular disorders Hypertension	7.0% 22/313 • Number of events 27 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	10.2% 32/313 • Number of events 34 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	11.6% 36/311 • Number of events 38 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Eye disorders Vitreous floaters	5.4% 17/313 • Number of events 25 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	3.5% 11/313 • Number of events 13 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	3.2% 10/311 • Number of events 13 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Infections and infestations Urinary tract infection	4.5% 14/313 • Number of events 23 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	4.8% 15/313 • Number of events 17 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	6.1% 19/311 • Number of events 22 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Injury, poisoning and procedural complications Fall	5.1% 16/313 • Number of events 16 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	6.1% 19/313 • Number of events 20 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	2.9% 9/311 • Number of events 9 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Investigations Intraocular pressure increased	5.4% 17/313 • Number of events 28 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	4.2% 13/313 • Number of events 25 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.	3.5% 11/311 • Number of events 13 • From Baseline until Week 100 Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER