Trial Outcomes & Findings for A Phase 3 Open-label Interventional Study of Intravenous Recombinant Coagulation Factor VIII Fc-von Willebrand Factor-XTEN Fusion Protein, Efanesoctocog Alfa (BIVV001), in Patients With Severe Hemophilia A (NCT NCT04161495)

NCT ID: NCT04161495

Last Updated: 2025-09-17

Results Overview

ABR is annualized number of treated bleeding episodes (BE) per participant per year. Treated Bleeding episode: any occurrence of hemorrhage that required administration of BIVV001. It started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode, any subsequent bleeding at same location/injections administered less than or equal to (\<=) 72 hours apart from previous injection were considered same bleeding episode. ABR=number of treated BE during efficacy period (EP)/number of days during EP\*365.25. EP reflects the sum of all intervals of time during which participants were treated with BIVV001 according to the study arms and treatment regimens. This outcome measure (OM) presents estimated results (i.e., results estimated by fitting negative binomial \[NB\] regression model on data collected during EP).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 159 participants
• Primary outcome timeframe: Baseline to Week 52
• Results posted on: 2025-09-17

Participant Flow

Study was conducted at 51 active sites in 19 countries. A total of 170 participants were screened between 19 November 2019 to 19 March 2021, of which 11 had screen failure due to not meeting the eligibility criteria.

A total of 159 participants were enrolled in this current study (EFC16293), of which 92 participants were rolled over from study OBS16221 and then subsequently enrolled and received BIVV001 in current study.

Participant milestones

Measure	Arm A: Prophylaxis Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 international units per kilogram (IU/kg) intravenous (IV) injection once-weekly (QW) for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis \[OBS16221\]) in the outcome measure analysis.	Arm B: On-Demand Then Prophylaxis Participants who were on an on-demand treatment regimen with a FVIII product prior to study EFC16293, including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection as an on-demand treatment (as needed for the treatment of bleeding episodes) from Week 1 to Week 26 in current study. At Week 26, participants in Arm B were switched to prophylaxis treatment, and received BIVV001 50 IU/kg, IV injection QW until Week 52.
Overall Study STARTED	133	26
Overall Study Historical Prophylaxis in OBS16221	82	10
Overall Study Arm B: On-demand	0	26
Overall Study Arm B: Prophylaxis	0	26
Overall Study COMPLETED	124	25
Overall Study NOT COMPLETED	9	1

Reasons for withdrawal

Measure	Arm A: Prophylaxis Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 international units per kilogram (IU/kg) intravenous (IV) injection once-weekly (QW) for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis \[OBS16221\]) in the outcome measure analysis.	Arm B: On-Demand Then Prophylaxis Participants who were on an on-demand treatment regimen with a FVIII product prior to study EFC16293, including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection as an on-demand treatment (as needed for the treatment of bleeding episodes) from Week 1 to Week 26 in current study. At Week 26, participants in Arm B were switched to prophylaxis treatment, and received BIVV001 50 IU/kg, IV injection QW until Week 52.
Overall Study Withdrawal by Subject	3	0
Overall Study Protocol Violation	1	0
Overall Study Prohibited concomitant medication	3	0
Overall Study Adverse Event	1	0
Overall Study Other - Unspecified	1	0
Overall Study Death	0	1

Baseline Characteristics

A Phase 3 Open-label Interventional Study of Intravenous Recombinant Coagulation Factor VIII Fc-von Willebrand Factor-XTEN Fusion Protein, Efanesoctocog Alfa (BIVV001), in Patients With Severe Hemophilia A

Baseline characteristics by cohort

Measure	Arm A: Prophylaxis n=133 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm B: On-Demand Then Prophylaxis n=26 Participants Participants who were on an on-demand treatment regimen with a FVIII product prior to study EFC16293, including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection as an on-demand treatment (as needed for the treatment of bleeding episodes) from Week 1 to Week 26 in current study. At Week 26, participants in Arm B were switched to prophylaxis treatment, and received BIVV001 50 IU/kg, IV injection QW until Week 52.	Total Title n=159 Participants
Age, Continuous	33.9 years STANDARD_DEVIATION 15.3 • n=93 Participants	42.8 years STANDARD_DEVIATION 11.7 • n=4 Participants	35.4 years STANDARD_DEVIATION 15.1 • n=27 Participants
Sex: Female, Male Female	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Sex: Female, Male Male	132 Participants n=93 Participants	26 Participants n=4 Participants	158 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	29 Participants n=93 Participants	0 Participants n=4 Participants	29 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	3 Participants n=93 Participants	0 Participants n=4 Participants	3 Participants n=27 Participants
Race (NIH/OMB) White	71 Participants n=93 Participants	26 Participants n=4 Participants	97 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	30 Participants n=93 Participants	0 Participants n=4 Participants	30 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: Analysis was performed on full analysis set (FAS) which included all participants who received at least 1 dose of study drug. Data for this OM was not planned to be collected and analyzed for Arm B.

ABR is annualized number of treated bleeding episodes (BE) per participant per year. Treated Bleeding episode: any occurrence of hemorrhage that required administration of BIVV001. It started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode, any subsequent bleeding at same location/injections administered less than or equal to (<=) 72 hours apart from previous injection were considered same bleeding episode. ABR=number of treated BE during efficacy period (EP)/number of days during EP*365.25. EP reflects the sum of all intervals of time during which participants were treated with BIVV001 according to the study arms and treatment regimens. This outcome measure (OM) presents estimated results (i.e., results estimated by fitting negative binomial [NB] regression model on data collected during EP).

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=133 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Estimated Annualized Bleeding Rate (ABR) in Arm A: Prophylaxis	—	0.71 episodes per participant per year Interval 0.52 to 0.97	—

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: Analysis was performed on FAS population. Data for this OM was not planned to be collected and analyzed for Arm B.

ABR is annualized number of treated bleeding episodes per participant per year. Treated Bleeding episode: any occurrence of hemorrhage that required administration of BIVV001. It started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode, any subsequent bleeding at same location/injections administered <=72 hours apart from previous injection were considered same bleeding episode. ABR=number of treated bleeding episodes during EP/number of days during EP*365.25. EP reflects the sum of all intervals of time during which participants were treated with BIVV001 according to the study arms and treatment regimens. This OM presents observed results (i.e., descriptive statistics values based on the data which was collected during EP).

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=133 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Observed Annualized Bleeding Rate in Arm A: Prophylaxis	—	0.71 episodes per participant per year Standard Deviation 1.43	—

SECONDARY outcome

Timeframe: Historical prophylaxis: From 6 months (prior to entry into study EFC16293) until the day before enrollment in EFC16293; BIVV001 prophylaxis: Baseline up to Week 52 of current study EFC16293

Population: Analysis was performed on per protocol set which included all participants who had received at least one dose of study drug and did not had important protocol deviations potentially impacting efficacy. Data for this OM was not planned to be collected and analyzed for Arm B.

ABR is annualized number of treated bleeding episodes per participant per year. Treated Bleeding episode: any occurrence of hemorrhage that required administration of BIVV001. It started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode, any subsequent bleeding at same location/injections administered <=72 hours apart from previous injection were considered same bleeding episode. ABR=number of treated bleeding episodes during EP/number of days during EP*365.25. EP reflects the sum of all intervals of time during which participants were treated with BIVV001 according to the study arms and treatment regimens. This OM presents estimated results (i.e., results received estimated by fitting NB regression model on data collected during EP).

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=77 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 n=77 Participants Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Estimated Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Non-inferiority Analysis	—	2.99 episodes per participant per year Interval 2.03 to 4.42	0.69 episodes per participant per year Interval 0.43 to 1.12

SECONDARY outcome

Timeframe: Historical prophylaxis: From 6 months (prior to entry into study EFC16293) until the day before enrollment in EFC16293; BIVV001 Prophylaxis: Baseline up to Week 52 of current study EFC16293

Population: Analysis was performed on per protocol set. Data for this OM was not planned to be collected and analyzed for Arm B.

ABR is annualized number of treated bleeding episodes per participant per year. Treated Bleeding episode: any occurrence of hemorrhage that required administration of BIVV001. It started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode, any subsequent bleeding at same location/injections administered <=72 hours apart from previous injection were considered same bleeding episode. ABR=number of treated bleeding episodes during EP/number of days during EP*365.25. EP reflects the sum of all intervals of time during which participants were treated with BIVV001 according to the study arms and treatment regimens. This OM presents observed results (i.e., descriptive statistics values based on the data which was collected during EP).

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=77 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 n=77 Participants Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Observed Annualized Bleeding Rate During the Efficacy Period in Prophylaxis - Non-inferiority Analysis	—	2.98 episodes per participant per year Standard Deviation 5.21	0.69 episodes per participant per year Standard Deviation 1.51

SECONDARY outcome

Timeframe: Historical Prophylaxis: From 6 months (prior to entry into study EFC16293) until the day before enrollment in EFC16293; BIVV001 Prophylaxis: Baseline up to Week 52 of current study EFC16293

Population: Analysis was performed on FAS population. Data for this OM was not planned to be collected and analyzed for Arm B.

ABR is annualized number of treated bleeding episodes per participant per year. Treated Bleeding episode: any occurrence of hemorrhage that required administration of BIVV001. It started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode, any subsequent bleeding at same location/injections administered <=72 hours apart from previous injection were considered same bleeding episode. ABR=number of treated bleeding episodes during EP/number of days during EP*365.25. EP reflects the sum of all intervals of time during which participants were treated with BIVV001 according to the study arms and treatment regimens. This OM presents estimated results (i.e., results received estimated by fitting NB regression model on data collected during EP).

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=78 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 n=78 Participants Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Estimated Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Superiority Analysis	—	2.96 episodes per participant per year Interval 2.0 to 4.37	0.69 episodes per participant per year Interval 0.43 to 1.11

SECONDARY outcome

Timeframe: Historical Prophylaxis: From 6 months (prior to entry into study EFC16293) until the day before enrollment in EFC16293; BIVV001 Prophylaxis: Baseline up to Week 52 of current study EFC16293

Population: Analysis was performed on FAS population. Data for this OM was not planned to be collected and analyzed for Arm B.

ABR is annualized number of treated bleeding episodes per participant per year. Treated Bleeding episode: any occurrence of hemorrhage that required administration of BIVV001. It started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode, any subsequent bleeding at same location/injections administered <=72 hours apart from previous injection were considered same bleeding episode. ABR=number of treated bleeding episodes during EP/number of days during EP*365.25. EP reflects the sum of all intervals of time during which participants were treated with BIVV001 according to the study arms and treatment regimens. This OM presents observed results (i.e., descriptive statistics values based on the data which was collected during EP).

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=78 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 n=78 Participants Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Observed Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Superiority Analysis	—	2.95 episodes per participant per year Standard Deviation 5.19	0.68 episodes per participant per year Standard Deviation 1.50

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on FAS population. Here, 'overall number of participants analyzed' = participants with available data for this OM. Data for this OM was not planned to be collected and analyzed for Arm B.

Haem-A-QoL is a participant-reported questionnaire designed for adult participants (greater than or equal to [>=] 17 years of age) with hemophilia; and consisted of 46 items comprising 10 domains (physical health [5 items], feelings [4 items], view of self [5 items], sports and leisure [5 items], work and school [4 items], dealing with hemophilia [3 items], treatment [8 items], future [5 items], family planning [4 items], partnership and sexuality [3 items]). Items were rated along five response options: never, rarely, sometimes, often, or all the time. Raw score for physical health domain were transformed to a scale ranged from 0 to 100, where lower scores denoted better physical health. Change from baseline in physical Health domain score was reported in this OM.

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=98 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Change From Baseline in Hemophilia-specific Health-related Quality of Life Questionnaire for Adults (Haem-A-QOL) Physical Health Domain Score at Week 52 in Arm A: Prophylaxis	—	-6.79 score on a scale Standard Deviation 18.59	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on FAS population. Here, 'overall number of participants analyzed' = participants with available data for this OM. Data for this OM was not planned to be collected and analyzed for Arm B.

PROMIS is a system of reliable and precise measures of participant-reported heath status. PROMIS measures cover physical, mental and social health and can be used for many chronic conditions. PROMIS - Pain Intensity - Short Form 3a consisted of 3 questions, participants reported for the intensity of pain experienced in the past 7 days. Each question had 5 responses scored between 1 (had no pain) to 5 (very severe pain). Total PROMIS pain intensity 3a score range was from 3 (no pain) to 15 (very severe pain), where higher score indicated more intense pain. Total raw score was converted into a T-score which rescaled raw score into standardized score with mean of 50 and standard deviation (SD) of 10. Higher PROMIS T-score represented worst outcome. For PROMIS pain intensity 3a, T-score of 60 was one SD worse than average.

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=119 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Change From Baseline in Patient Reported Outcomes Measurements Information Systems (PROMIS) Pain Intensity 3a Score at Week 52 in Arm A: Prophylaxis	—	-1.97 T-score Standard Deviation 7.86	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on FAS population. Here, 'overall number of participants analyzed' = participants with available data for this OM. Data for this OM was not planned to be collected and analyzed for Arm B.

HJHS is a validated 11-item scoring tool developed for the assessment of joint health in participants with hemophilia. It comprised an evaluation of the elbows, knee and ankle joints: swelling (0 to 3), duration of swelling (0 and 1), muscle atrophy (0 to 2), crepitus on motion (0 to 2), flexion loss (0 to 3), extension loss (0 to 3), joint pain (0 to 2) and strength (0 to 4), in each item 0 = none and higher score = severe damage and global gait (walking, stairs, running, hopping on 1 leg) scored on scale ranged from 0 to 4, where 0 = all skills in normal limit and 4 = no skills within normal limits). Total HJHS score = sum of joint totals (0 to 120) + general gait (1 to 4) and ranged from 0 (no joint damage) to 124 (severe joint damage), where higher score indicated severe joint damage.

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=107 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Change From Baseline in Hemophilia Joint Health Score (HJHS) Total Score at Week 52 in Arm A: Prophylaxis	—	-1.5 score on a scale Standard Deviation 6.4	—

SECONDARY outcome

Timeframe: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52

Population: Analysis was performed on FAS. Data for this OM was planned to be collected and analyzed separately in Arm B for participants during on-demand treatment and during prophylaxis treatment post switch.

ABR: annualized number of treated bleeding episodes per participant per year. EP reflects sum of all intervals of time during which participants were treated with BIVV001 according to study arms and treatment regimens. Treated bleeding episode: episode that started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode, any subsequent bleeding at same location/injections administered <=72 hours apart from previous injection were considered same bleeding episode. Any bleed at different location was considered as separate bleeding episode, regardless of time from last injection. Spontaneous bleeding: bleeding episode without contributing factor (definite trauma/antecedent "strenuous" activity). Traumatic bleeding: bleeding episode with known/believed reason for bleed.

Outcome measures

Measure	Arm B: Prophylaxis n=26 Participants Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=133 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 n=26 Participants Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type) Spontaneous	0.00 episodes per participant per year Interval 0.0 to 0.0	0.00 episodes per participant per year Interval 0.0 to 0.0	16.69 episodes per participant per year Interval 8.64 to 23.76
Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type) Traumatic	0.00 episodes per participant per year Interval 0.0 to 0.0	0.00 episodes per participant per year Interval 0.0 to 0.0	3.95 episodes per participant per year Interval 0.0 to 6.48
Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type) Unknown type	0.00 episodes per participant per year Interval 0.0 to 0.0	0.00 episodes per participant per year Interval 0.0 to 0.0	0.00 episodes per participant per year Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52

Population: Analysis was performed on FAS. Data for this OM was planned to be collected and analyzed separately in Arm B for participants during on-demand treatment and during prophylaxis treatment post switch.

ABR: annualized number of treated bleeding episodes per participant per year. Efficacy period reflects sum of all intervals of time during which participants were treated with BIVV001 according to study arms and treatment regimens. Treated bleeding episode: episode that started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode, any subsequent bleeding at same location/injections administered <=72 hours apart from previous injection were considered same bleeding episode. Any bleed at different location was considered as separate bleeding episode, regardless of time from last injection. Spontaneous bleeding: bleeding episode without contributing factor (definite trauma/antecedent "strenuous" activity). Traumatic bleeding: bleeding episode with known/believed reason for bleed.

Outcome measures

Measure	Arm B: Prophylaxis n=26 Participants Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=133 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 n=26 Participants Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa) Joint	0.00 episodes per participant per year Interval 0.0 to 0.0	0.00 episodes per participant per year Interval 0.0 to 1.02	18.42 episodes per participant per year Interval 10.8 to 23.9
Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa) Muscle	0.00 episodes per participant per year Interval 0.0 to 0.0	0.00 episodes per participant per year Interval 0.0 to 0.0	0.00 episodes per participant per year Interval 0.0 to 4.15
Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa) Internal	0.00 episodes per participant per year Interval 0.0 to 0.0	0.00 episodes per participant per year Interval 0.0 to 0.0	0.00 episodes per participant per year Interval 0.0 to 0.0
Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa) Skin/mucosa	0.00 episodes per participant per year Interval 0.0 to 0.0	0.00 episodes per participant per year Interval 0.0 to 0.0	0.00 episodes per participant per year Interval 0.0 to 2.09

SECONDARY outcome

Timeframe: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52

Population: Analysis was performed on FAS population. Data for this OM was planned to be collected and analyzed separately in Arm B for participants during on-demand treatment and during prophylaxis treatment post switch.

ABR: annualized number of all bleeding (treated and untreated) episodes/participant/year. ABR = number of all bleeding episodes during EP/number of days in EP*365.25. EP reflects sum of all time intervals during which participants were treated with BIVV001 according to study arms and treatment regimens. Bleeding episode: episode started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode, any subsequent bleeding at same location/injections administered <=72 hours apart from previous injection were considered same bleeding episode. Any bleed at different location: considered as separate bleeding episode, regardless of time from last injection. Spontaneous: bleeding without contributing factor (definite trauma/antecedent "strenuous" activity). Traumatic: bleeding with known/believed reason.

Outcome measures

Measure	Arm B: Prophylaxis n=26 Participants Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=133 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 n=26 Participants Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Annualized Bleeding Rate for All Bleeding Episodes	0.00 episodes per participant per year Interval 0.0 to 1.93	0.00 episodes per participant per year Interval 0.0 to 1.15	21.13 episodes per participant per year Interval 16.8 to 27.13

SECONDARY outcome

Timeframe: Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52

Population: Analysis was performed on FAS population. In this OM, ABR of Arm B: separately for participants during prophylaxis treatment versus On-Demand treatment was reported.

ABR is annualized number of treated bleeding episodes per participant per year. Treated Bleeding episode: any occurrence of hemorrhage that required administration of BIVV001. It started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode, any subsequent bleeding at same location/injections administered <=72 hours apart from previous injection were considered same bleeding episode. ABR = (Number of treated bleeding episodes during EP/number of days during EP*365.25. EP reflects the sum of all intervals of time during which participants were treated with BIVV001 according to the study arms and treatment regimens.

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=26 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 n=26 Participants Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Annualized Bleeding Rate: Intra-participant Comparison of Arm B Participants	—	21.13 episodes per participant per year Interval 15.12 to 27.13	0.00 episodes per participant per year Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Analysis was performed on pharmacokinetic (PK) analysis set which included participants who had completed adequate blood sample collection to assess key PK parameters. Here, 'overall number of participants analyzed' = participants with available data for this OM. Data for this OM was not planned to be collected and analyzed for Arm B.

FVIII activity level was measured using activated partial thromboplastin time (aPTT)-based one stage clotting assay. Percentage of participants who achieved steady-state trough FVIII activity levels above (>) 1%, 5%, 10%, 15%, and 20% were reported for Arm A: Prophylaxis in this OM. Participants were counted in more than one row, as applicable.

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=131 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Percentage of Participants Achieving Factor VIII (FVIII) Activity Levels Above 1%, 5%, 10%, 15%, and 20% in Arm A: Prophylaxis >1%	—	100 percentage of participants	—
Percentage of Participants Achieving Factor VIII (FVIII) Activity Levels Above 1%, 5%, 10%, 15%, and 20% in Arm A: Prophylaxis >5%	—	99.0 percentage of participants	—
Percentage of Participants Achieving Factor VIII (FVIII) Activity Levels Above 1%, 5%, 10%, 15%, and 20% in Arm A: Prophylaxis >10%	—	83.5 percentage of participants	—
Percentage of Participants Achieving Factor VIII (FVIII) Activity Levels Above 1%, 5%, 10%, 15%, and 20% in Arm A: Prophylaxis >15%	—	40.8 percentage of participants	—
Percentage of Participants Achieving Factor VIII (FVIII) Activity Levels Above 1%, 5%, 10%, 15%, and 20% in Arm A: Prophylaxis >20%	—	17.5 percentage of participants	—

SECONDARY outcome

Timeframe: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52

Population: Analysis was performed on FAS population. Here, 'overall number of participants analyzed' = participants with available data for this OM. Data for this OM was planned to be collected and analyzed separately in Arm B for participants during on-demand treatment and during prophylaxis treatment post switch.

The number of injections required to resolve each bleeding episode was averaged across all bleeding episodes per participant. A bleeding episode was defined as an episode that started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode, any subsequent bleeding at same location or injections administered <=72 hours apart from previous injection were considered same bleeding episode.

Outcome measures

Measure	Arm B: Prophylaxis n=6 Participants Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=47 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 n=26 Participants Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Number of Injections of BIVV001 Required to Treat a Bleeding Episode	1.0 injections per participant Interval 1.0 to 1.0	1.0 injections per participant Interval 1.0 to 1.0	1.0 injections per participant Interval 1.0 to 1.0

SECONDARY outcome

Timeframe: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52

Population: Analysis was performed on FAS population. Here, 'overall number of participants analyzed' = participants with available data for this OM and 'overall number of units analyzed' = total number of treated bleeding episodes. Data for this OM was planned to be collected and analyzed separately in Arm B for participants during on-demand treatment and during prophylaxis treatment post switch.

The total dose (IU/kg) used to resolve each bleeding episode was averaged across all bleeding episodes per participant. A bleeding episode was defined as an episode that started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode, any subsequent bleeding at same location or injections administered <=72 hours apart from previous injection were considered same bleeding episode.

Outcome measures

Measure	Arm B: Prophylaxis n=8 Treated bleeding episode Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=86 Treated bleeding episode Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 n=268 Treated bleeding episode Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Total Dose of BIVV001 Required to Treat Bleeding Episode	49.79 IU/kg Interval 40.54 to 50.6	50.85 IU/kg Interval 41.69 to 52.08	50.96 IU/kg Interval 50.1 to 51.83

SECONDARY outcome

Timeframe: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52

Population: Analysis was performed on FAS population. Here, 'Overall number of participants analyzed' = participants with available data for this OM and 'overall number of units analyzed' = total number of treated bleeding episodes. Data for this OM was planned to be collected and analyzed separately in Arm B for participants during on-demand treatment and during prophylaxis treatment post switch.

A bleeding episode was defined as an episode that started from 1st sign of bleed and ended no more than 72 hours after last injection to treat bleeding episode, any subsequent bleeding at same location or injections administered <=72 hours apart from previous injection were considered same bleeding episode. Percentage of bleeding episodes (of all bleeding episodes occurred) which were treated with single injection was reported in this OM.

Outcome measures

Measure	Arm B: Prophylaxis n=8 Treated bleeding episode Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=86 Treated bleeding episode Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 n=268 Treated bleeding episode Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Percentage of Bleeding Episodes Treated With a Single Injection of BIVV001	100 percentage of bleeding episodes	94.2 percentage of bleeding episodes	97.4 percentage of bleeding episodes

SECONDARY outcome

Timeframe: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52

Population: Analysis was performed on FAS population. Here, 'Overall number of participants analyzed' = participants with available data for this OM. Data for this OM was planned to be collected and analyzed separately in Arm B for participants during on-demand treatment and during prophylaxis treatment post switch.

The participant's response related to each injection of BIVV001 treatment for treating a bleed was evaluated using ISTH 4-point response scale categorized as: Excellent (complete pain relief/complete resolution of signs of bleeding), Good (significant pain relief/improvement in signs of bleeding), Moderate (modest pain relief/improvement in signs of bleeding) and none (no or minimal improvement/condition worsened). Assessment was performed approximately 72 hours after the initial treatment for the bleeding episode. Bleeding episode was defined as an episode that started from first sign of a bleed and ended no more than 72 hours after last treatment for bleed, within which any symptoms of bleeding at same location or injections <=72 hours apart were considered same bleeding episode. Participants were counted in more than one row, as applicable.

Outcome measures

Measure	Arm B: Prophylaxis n=6 Participants Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=47 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 n=26 Participants Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Percentage of Participants With Response to BIVV001 Treatment Based on the International Society on Thrombosis and Haemostasis (ISTH) 4-point Response Scale Excellent or Good	100 percentage of participants	82.2 percentage of participants	98.4 percentage of participants
Percentage of Participants With Response to BIVV001 Treatment Based on the International Society on Thrombosis and Haemostasis (ISTH) 4-point Response Scale Excellent	83.3 percentage of participants	53.4 percentage of participants	76.5 percentage of participants
Percentage of Participants With Response to BIVV001 Treatment Based on the International Society on Thrombosis and Haemostasis (ISTH) 4-point Response Scale Good	16.7 percentage of participants	28.8 percentage of participants	22.0 percentage of participants
Percentage of Participants With Response to BIVV001 Treatment Based on the International Society on Thrombosis and Haemostasis (ISTH) 4-point Response Scale Moderate	0 percentage of participants	13.7 percentage of participants	1.6 percentage of participants
Percentage of Participants With Response to BIVV001 Treatment Based on the International Society on Thrombosis and Haemostasis (ISTH) 4-point Response Scale None	0 percentage of participants	4.1 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52

Population: Analysis was performed on FAS population. Data for this OM was planned to be collected and analyzed separately in Arm B for participants during on-demand treatment and during prophylaxis treatment post switch.

Physicians assessed participant's response to BIVV001 treatment using 4-point response scale: Excellent=bleeding episodes (BE) responded to fewer than/usual number of injections/less than/usual dose of FVIII/rate of breakthrough bleeding during prophylaxis was <= that usually observed; Effective = most BE responded to same number of injections and dose, but some required more injections/higher doses/there was minor increase in rate of breakthrough bleeding; partially effective = BE most often required more injections and/or higher doses than expected/adequate breakthrough bleeding prevention during prophylaxis required more frequent injections and/or higher doses; Ineffective = routine failure to control hemostasis or hemostatic control required additional agents. Percentages were based on total number of responses.

Outcome measures

Measure	Arm B: Prophylaxis n=44 Total responses Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=622 Total responses Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 n=77 Total responses Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Physicians' Global Assessment of Participant's Response to BIVV001 Treatment Excellent	93.2 percentage of responses	95.7 percentage of responses	96.1 percentage of responses
Physicians' Global Assessment of Participant's Response to BIVV001 Treatment Effective	6.8 percentage of responses	4.3 percentage of responses	3.9 percentage of responses
Physicians' Global Assessment of Participant's Response to BIVV001 Treatment Partially effective	0 percentage of responses	0 percentage of responses	0 percentage of responses
Physicians' Global Assessment of Participant's Response to BIVV001 Treatment Ineffective	0 percentage of responses	0 percentage of responses	0 percentage of responses

SECONDARY outcome

Timeframe: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52

Population: Analysis was performed on FAS population. Data for this OM was planned to be collected and analyzed separately in Arm B for participants during on-demand treatment and during prophylaxis treatment post switch.

Total annualized BIVV001 consumption (in IU/kg) was calculated for each participant as: Total IU/kg of BIVV001 during EP divided by total number of days during EP*365.25. EP reflects the sum of all intervals of time during which participants were treated with BIVV001 according to the study arms and treatment regimens.

Outcome measures

Measure	Arm B: Prophylaxis n=26 Participants Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=133 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 n=26 Participants Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Total Annualized BIVV001 Consumption Per Participant	2737.53 IU/kg per participant per year Interval 2486.4 to 2924.8	2756.99 IU/kg per participant per year Interval 2385.1 to 50171.7	1212.27 IU/kg per participant per year Interval 435.9 to 2023.8

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on FAS population. Here, 'number analyzed' = participants with available data for each specified category. Data for this OM was not planned to be collected and analyzed for Arm B.

HJHS is a validated 11-item scoring tool developed for the assessment of joint health in participants with hemophilia. Following domains were assessed for elbows, knee and ankle joints: swelling (score 0 = no swelling to 3=severe), duration of swelling (score 0 = no swelling and 1 = >=6 months), muscle atrophy (score 0 = none to 2 = severe), crepitus on motion (score 0 = none to 2=severe), flexion loss (score 0 = <5' to 3 = >20'), extension loss (score 0 = <5' to 3 = >20'), joint pain (score 0 = no pain through active range of motion to 2 = pain through active range) and strength (score 0 = holds test position with maximum resistance to 4 = trace/no muscle contraction), in each item 0 = none and higher score = severe damage.

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=133 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Change From Baseline in Hemophilia Joint Health Score (HJHS) Domain Score at Week 52 in Arm A: Prophylaxis Swelling	—	-0.3 score on scale Standard Deviation 1.2	—
Change From Baseline in Hemophilia Joint Health Score (HJHS) Domain Score at Week 52 in Arm A: Prophylaxis Duration Of Swelling	—	-0.2 score on scale Standard Deviation 0.8	—
Change From Baseline in Hemophilia Joint Health Score (HJHS) Domain Score at Week 52 in Arm A: Prophylaxis Muscle Atrophy	—	-0.3 score on scale Standard Deviation 1.2	—
Change From Baseline in Hemophilia Joint Health Score (HJHS) Domain Score at Week 52 in Arm A: Prophylaxis Crepitus On Motion	—	-0.3 score on scale Standard Deviation 1.2	—
Change From Baseline in Hemophilia Joint Health Score (HJHS) Domain Score at Week 52 in Arm A: Prophylaxis Flexion Loss	—	-0.3 score on scale Standard Deviation 1.6	—
Change From Baseline in Hemophilia Joint Health Score (HJHS) Domain Score at Week 52 in Arm A: Prophylaxis Extension Loss	—	-0.2 score on scale Standard Deviation 1.5	—
Change From Baseline in Hemophilia Joint Health Score (HJHS) Domain Score at Week 52 in Arm A: Prophylaxis Joint Pain	—	-0.1 score on scale Standard Deviation 1.2	—
Change From Baseline in Hemophilia Joint Health Score (HJHS) Domain Score at Week 52 in Arm A: Prophylaxis Strength	—	0.3 score on scale Standard Deviation 0.6	—

SECONDARY outcome

Timeframe: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52

Population: Analysis was performed on FAS population. Data for this OM was planned to be collected and analyzed separately in Arm B for participants during on-demand treatment and during prophylaxis treatment post switch.

AJBR: annualized number of joint bleeding/participant/year. ABR = number of treated joint bleeding episodes during EP divided by total number of days during EP*365.25. Joint bleeding episode: an unusual sensation in joint ('aura') in combination with 1) increasing swelling/warmth over skin, joint; 2) increasing pain or 3) progressive loss of range of motion or difficulty in using limb as compared with Baseline. Bleeding episode (BE): episode that started from first sign of bleed and ended no more than 72 hours after last treatment for bleed, within which any symptoms of bleeding at same location/injections <=72 hours apart were considered same bleeding episode. EP reflects the sum of all intervals of time during which participants were treated with BIVV001 according to study arms and treatment regimens.

Outcome measures

Measure	Arm B: Prophylaxis n=26 Participants Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=133 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 n=26 Participants Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Estimated Annualized Joint Bleeding Rate (AJBR)	0.62 joint BE per participant per year Interval 0.25 to 1.52	0.51 joint BE per participant per year Interval 0.36 to 0.72	17.48 joint BE per participant per year Interval 14.88 to 20.54

SECONDARY outcome

Timeframe: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52

Population: Analysis was performed on FAS population. Data for this OM was planned to be collected and analyzed separately in Arm B for participants during on-demand treatment and during prophylaxis treatment post switch.

AJBR: annualized number of joint bleeding/participant/year. ABR = number of treated joint bleeding episodes during EP divided by total number of days during EP*365.25. Joint bleeding episode: unusual sensation in joint ('aura') with 1) in combination with increasing swelling/warmth over skin, joint; 2) increasing pain or 3) progressive loss of range of motion or difficulty in using limb as compared with Baseline. BE: episode that started from first sign of bleed and ended no more than 72 hours after last treatment for bleed, within which any symptoms of bleeding at same location/injections <= 72 hours apart were considered same bleeding episode. EP reflects sum of all intervals of time during which participants were treated with BIVV001 according to study arms and treatment regimens.

Outcome measures

Measure	Arm B: Prophylaxis n=26 Participants Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=133 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 n=26 Participants Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Observed Annualized Joint Bleeding Rate (AJBR)	0.61 joint BE per participant per year Standard Deviation 1.33	0.52 joint BE per participant per year Standard Deviation 1.09	17.45 joint BE per participant per year Standard Deviation 7.31

SECONDARY outcome

Timeframe: Week 52

Population: Analysis was performed on FAS population. Here, 'overall number of participants analyzed' = participants with available data for this OM and 'overall number of units analyzed' = total number of evaluable target joints with \>=3 spontaneous bleeding at Baseline and with 12 months continuous exposure. Data for this OM was not planned to be collected and analyzed for Arm B.

A target joint at baseline was defined as a major joint with >=3 spontaneous bleeding episodes in a consecutive 6 month period prior to entry to the study, captured at Baseline. A target joint resolved was defined as <=2 spontaneous bleeds into that joint during 12 months of continuous exposure. Total number of target joints resolved at Week 52 were reported.

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=45 Total number of evaluable target joints Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Total Number of Target Joint Resolved in Participants at Week 52 in Arm A: Prophylaxis	—	45 Target joints resolved	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on FAS population. Here, 'overall number of participants analyzed' = participants with available data for this OM. Data for this OM was not planned to be collected and analyzed for Arm B.

Haem-A-QoL: participant-reported questionnaire designed for adult participants (>=17 years of age) with hemophilia; and consisted of 46 items comprising 10 domains (physical health [5 items], feelings [4 items], view of self [5 items], sports and leisure [5 items], work and school [4 items], dealing with hemophilia [3 items], treatment [8 items], future [5 items], family planning [4 items], partnership and sexuality [3 items]). Items were rated along 5 response options: 1=never, 2=rarely, 3=sometimes,4=often, and 5=all the time and higher scores represent greater impairment. Raw score for each domain were transformed to a scale ranged between 0 and 100, where lower scores denoted better physical health. Haem-A-QoL Total Score was average of all domain scores and ranged from 0 to 100, where lower scores = better quality of life.

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=98 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Change From Baseline in Hemophilia-specific Health-related Quality of Life Questionnaire for Adults Total Score at Week 52 in Arm A: Prophylaxis	—	-4.56 score on scale Standard Deviation 11.15	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants with available data for this OM. Data for this OM was not planned to be collected and analyzed for Arm B.

PROMIS-SF v2.0 PF 6b consisted of 2-items from item-improved Health Assessment Questionnaire (HAQ) and 4-items from item-improved Physical Function-10 (PF-10) instruments. Both of these instruments assessed participant's present abilities and had 5-response options: HAQ: 1=without any difficulty, 2=with little difficulty, 3=with some difficulty, 4=with much difficulty,5=unable to do and PF-10: 1=not at all, 2=very little, 3=somewhat, 4=quite a lot, 5=cannot do. Total score of PROMIS-SF PF 6b: average scores of component items, which ranged from 0 (no disability) to 100 (worst disability). T-score rescales raw scale score (sum of scores from all questions answered) into a standardized score with a mean of 50 and standard deviation of 10, based on scoring tables provided in PROMIS Scoring Manuals. Higher PROMIS T-score=more of concept being measured.

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=97 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Change From Baseline in Patient Reported Outcomes Measurements Information Systems Short Form (PROMIS-SF) Physical Function (PF) 6b at Week 52 in Arm A: Prophylaxis	—	0.62 T-score Standard Deviation 4.77	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Analyzed on a surgery subgroup population which included all participants who had undergone major surgery after the 1st dose of study drug. Here, 'overall number of participants analyzed' = participants with major surgeries during the treatment regimen and 'overall number of units analyzed' = number of major surgeries during the treatment regimen occurred in participants analyzed.

The Investigators/Surgeons who complete the surgical procedures assess the participant's response to surgery with BIVV001 treatment using a 4-point scale, where responses were categorized as worst response: 1 = Excellent, 2 = Good, 3 = Fair, and 4 = Poor/none. Higher score indicated worst response. This assessment was performed 24 hours after the surgery. A surgery can be counted in more than one response category.

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=12 Number of major surgeries Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Investigators' or Surgeons' Assessment of Participant's Hemostatic Response to BIVV001 Treatment Excellent or Good	—	12 major surgeries	—
Investigators' or Surgeons' Assessment of Participant's Hemostatic Response to BIVV001 Treatment Excellent	—	12 major surgeries	—
Investigators' or Surgeons' Assessment of Participant's Hemostatic Response to BIVV001 Treatment Good	—	0 major surgeries	—
Investigators' or Surgeons' Assessment of Participant's Hemostatic Response to BIVV001 Treatment Fair	—	0 major surgeries	—
Investigators' or Surgeons' Assessment of Participant's Hemostatic Response to BIVV001 Treatment Poor/none	—	0 major surgeries	—

SECONDARY outcome

Timeframe: During the perioperative period (any time during Baseline up to Week 52)

Population: Analysis was performed on surgery subgroup population. Here, 'overall number of participants analyzed' = participants with major surgeries during the treatment regimen and 'overall number of units analyzed' = number of major surgeries during the treatment regimen occurred in participants analyzed.

Perioperative period was time lapse surrounding the surgical act which was divided into 3 stages: preoperative (4 weeks prior to surgery), operative (during the surgery) and post-operative (24-hour post-surgery). The number of injections to maintain hemostasis (a process to prevent and stop bleeding from a blood vessel) per surgery included all injections from loading dose (i.e., the preoperative injection, administered either on the day of surgery or one day prior to the surgery), to the end of surgery. Major surgery: defined as any invasive operative procedure that required any of the following: opening into major body cavity (e.g., abdomen, thorax, skull); operation on a joint; removal of an organ; dental extraction of any molar teeth or >=3 non-molar teeth; operative alteration of normal anatomy; crossing of a mesenchymal barrier (e.g., pleura, peritoneum, dura).

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=12 Number of major surgeries Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Number of Injections Per Surgery Required to Maintain Hemostasis During Perioperative Period for Major Surgery >Four injection	—	0 injections	—
Number of Injections Per Surgery Required to Maintain Hemostasis During Perioperative Period for Major Surgery Zero injection	—	1 injections	—
Number of Injections Per Surgery Required to Maintain Hemostasis During Perioperative Period for Major Surgery One injection	—	11 injections	—
Number of Injections Per Surgery Required to Maintain Hemostasis During Perioperative Period for Major Surgery Two injection	—	0 injections	—
Number of Injections Per Surgery Required to Maintain Hemostasis During Perioperative Period for Major Surgery Three injection	—	0 injections	—
Number of Injections Per Surgery Required to Maintain Hemostasis During Perioperative Period for Major Surgery Four injection	—	0 injections	—

SECONDARY outcome

Timeframe: Day -1 to Day 0 (day of surgery)

Population: Analysis was performed on surgery subgroup population. Here, 'overall number of participants analyzed' = participants with major surgeries during the treatment regimen and 'overall number of units analyzed' = number of major surgeries for which a loading dose was given on the day of surgery or one day prior to surgery (i.e. Day -1).

Perioperative period was time lapse surrounding surgical act which was divided into 3 stages: preoperative (4 weeks prior to surgery), operative (during the surgery) and post-operative (24-hour post-surgery). Total dose (IU/kg) was the sum across all injections per major surgery (including loading dose) needed to maintain hemostasis (a process to prevent and stop bleeding from a blood vessel) during surgery. Major surgery: defined as any invasive operative procedure that required any of the following: opening into major body cavity (e.g., abdomen, thorax, skull); operation on a joint; removal of an organ; dental extraction of any molar teeth or >=3 non-molar teeth; operative alteration of normal anatomy; crossing of a mesenchymal barrier (e.g., pleura, peritoneum, dura). Day 0 was defined as the surgery day. The loading dose for a given surgery was the preoperative injection, administered either on the day of surgery or one day prior to the surgery (i.e., Day -1).

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=11 Number of major surgeries Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Total Dose Required to Maintain Hemostasis From Day -1 to Day 0 During Perioperative Period for Major Surgery	—	41.65 IU/kg Standard Deviation 15.21	—

SECONDARY outcome

Timeframe: Day -1 to Day 14

Population: Analysis was performed on surgery subgroup population. Here, overall number of participants analyzed = participants with major surgeries during the treatment regimen and 'overall number of units analyzed' field = number of major surgeries with BIVV001 administration within Day -1 to Day 14.

Perioperative period: time lapse surrounding surgical act which was divided into 3 stages: preoperative (4 weeks prior to surgery), operative (during the surgery) and post-operative (24-hour post-surgery). Total BIVV001 consumption were summarized from the loading dose (the day before surgery, i.e, on Day -1) up to 2 weeks following the surgery (i.e., Day 14) and were reported in this OM.

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=12 Number of major surgeries Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Total BIVV001 Consumption From Day -1 to 14 During Perioperative Period for Major Surgery	—	166.71 IU/kg per major surgery Standard Deviation 72.48	—

SECONDARY outcome

Timeframe: During the perioperative period (any time during Baseline up to Week 52)

Population: Analysis was performed on surgery subgroup population. Here, overall number of participants analyzed = participants with major surgeries during the treatment regimen and 'overall number of units analyzed' = number of major surgeries during the treatment regimen occurred in participants analyzed.

The perioperative period was the time lapse surrounding the surgical act which was divided into 3 stages: preoperative (4 weeks prior to surgery), operative (during the surgery) and post-operative (24-hour post-surgery). The number of blood component transfusions used during perioperative period were summarized categorically (0, 1, 2, 3 and >3) for all major surgeries for the surgery subgroup. Major surgery: defined as any invasive operative procedure that required any of the following: opening into major body cavity (e.g., abdomen, thorax, skull); operation on a joint; removal of an organ; dental extraction of any molar teeth or >=3 non-molar teeth; operative alteration of normal anatomy; crossing of a mesenchymal barrier (e.g., pleura, peritoneum, dura).

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=12 Number of major surgeries Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Number of Blood Component Transfusions Used During Perioperative Period for Major Surgery Zero	—	12 transfusions per surgery	—
Number of Blood Component Transfusions Used During Perioperative Period for Major Surgery One	—	0 transfusions per surgery	—
Number of Blood Component Transfusions Used During Perioperative Period for Major Surgery Two	—	0 transfusions per surgery	—
Number of Blood Component Transfusions Used During Perioperative Period for Major Surgery Three	—	0 transfusions per surgery	—
Number of Blood Component Transfusions Used During Perioperative Period for Major Surgery >Three	—	0 transfusions per surgery	—

SECONDARY outcome

Timeframe: During the perioperative period (any time during Baseline up to Week 52)

Population: Analysis was performed on surgery subgroup population. Here, overall number of participants analyzed = participants with major surgeries during the treatment regimen and 'overall number of units analyzed' = number of major surgeries during the treatment regimen occurred in participants analyzed.

The perioperative period was the time lapse surrounding the surgical act which was divided into 3 stages: preoperative (4 weeks prior to surgery), operative (during the surgery) and post-operative (24-hour post-surgery). The type of blood component (Red blood cell, platelet, fresh frozen plasma, whole blood and other) transfusions used were summarized for all major surgeries. Post-operative referred to the day following the end of surgery to the date of hospital discharge. Major surgery: defined as any invasive operative procedure that required any of the following: opening into major body cavity (e.g., abdomen, thorax, skull); operation on a joint; removal of an organ; dental extraction of any molar teeth or >=3 non-molar teeth; operative alteration of normal anatomy; crossing of a mesenchymal barrier (e.g., pleura, peritoneum, dura).

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=12 Number of major surgeries Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Type of Blood Component Transfusions Used During Perioperative Period for Major Surgery Red Blood Cell	—	0 transfusions per surgery	—
Type of Blood Component Transfusions Used During Perioperative Period for Major Surgery Platelet	—	0 transfusions per surgery	—
Type of Blood Component Transfusions Used During Perioperative Period for Major Surgery Fresh Frozen Plasma	—	0 transfusions per surgery	—
Type of Blood Component Transfusions Used During Perioperative Period for Major Surgery Whole Blood	—	0 transfusions per surgery	—
Type of Blood Component Transfusions Used During Perioperative Period for Major Surgery Other	—	0 transfusions per surgery	—

SECONDARY outcome

Timeframe: Day 0 (i.e., day of surgery)

Population: Analysis was performed on surgery subgroup population. Here, overall number of participants analyzed = participants with reported blood loss during major surgery and 'overall number of units analyzed' = number of major surgeries with blood loss report during the treatment regimen occurred in participants analyzed.

The estimated total blood loss (in milliliters) during major surgeries were summarized. Major surgery: defined as any invasive operative procedure that required any of the following: opening into major body cavity (e.g., abdomen, thorax, skull); operation on a joint; removal of an organ; dental extraction of any molar teeth or >=3 non-molar teeth; operative alteration of normal anatomy; crossing of a mesenchymal barrier (e.g., pleura, peritoneum, dura).

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=6 number of major surgery with blood loss Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Estimated Blood Loss During Major Surgery	—	143.33 milliliters Standard Deviation 189.38	—

SECONDARY outcome

Timeframe: Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 up to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55)

Population: Analysis was performed on safety population which included all participants who received at least one dose of study drug. Data for this OM was planned to be collected and analyzed separately in Arm B for participants during on-demand treatment and during prophylaxis treatment post switch.

An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug which did not necessarily have a causal relationship with the treatment. A serious AE (SAE) was defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly or birth defect, or was a medically important event. Treatment-emergent AEs were AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose.

Outcome measures

Measure	Arm B: Prophylaxis n=26 Participants Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=133 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 n=26 Participants Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAE) TEAE	8 Participants	108 Participants	12 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAE) TESAE	0 Participants	13 Participants	2 Participants

SECONDARY outcome

Timeframe: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52

Population: Analysis was performed on safety population. Data for this OM was planned to be collected and analyzed separately in Arm B for participants during on-demand treatment and during prophylaxis treatment post switch.

Development of inhibitors was defined as an inhibitor result of >=0.6 bethesda unit per milliliter (BU/mL) that was confirmed by a second test result of >=0.6 BU/mL from a separate sample, drawn 2 to 4 weeks following the date when the original sample was drawn. Both tests must have been performed by the central laboratory using the Nijmegen-modified Bethesda assay.

Outcome measures

Measure	Arm B: Prophylaxis n=26 Participants Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=133 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 n=26 Participants Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Number of Participants With Neutralizing Antibodies (Development of Inhibitors) Directed Against Factor VIII	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Arm A: Baseline to Week 52; Arm B: On-demand - Baseline to Week 26, Prophylaxis - Week 26 to 52

Population: Analysis was performed on safety population. Data for this OM was planned to be collected and analyzed separately in Arm B for participants during on-demand treatment and during prophylaxis treatment post switch.

Embolic and thrombotic events were defined as arterial or venous thrombosis, confirmed by imaging.

Outcome measures

Measure	Arm B: Prophylaxis n=26 Participants Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=133 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 n=26 Participants Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Number of Participants With Occurrence of Embolic and Thrombotic Events	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (15 minutes post-dose on Day 1) and 15 minutes post-dose on Week 52

Population: Analysis was performed on PK population which included all participants who had completed adequate blood sample collection to assess key PK parameters. Here, 'number analyzed' = participants with available data for each specified category.

Cmax was defined as the maximum observed plasma FVIII Activity.

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=133 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 n=26 Participants Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Pharmacokinetics (PK): Maximum FVIII Activity (Cmax) Baseline	—	125.05 IU per deciliter Standard Deviation 31.72	138.36 IU per deciliter Standard Deviation 48.66
Pharmacokinetics (PK): Maximum FVIII Activity (Cmax) Week 52	—	144.72 IU per deciliter Standard Deviation 36.65	149.42 IU per deciliter Standard Deviation 29.63

SECONDARY outcome

Timeframe: pre-dose, 0.25, 3, 24, 72, 168, 240 and 336 hours post-dose on Day 1 (Baseline); pre-dose, 0.25, 3, 24, 72, 168, 240, and 336 hours post-dose on Week 26

Population: Analysis was performed on PK population. Here, 'number analyzed' = participants with available data for each specified category. Data for this OM was planned to be collected and analyzed for combined population of Arm A and B. For Week 26, PK samples were collected and analyzed for arm A only as per protocol.

Plasma t1/2z was the time measured for the plasma concentration of drug to decrease by one half. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Baseline and at Week 26; however, participants did not receive BIVV001 dose in week 2 and week 27.

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=159 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Pharmacokinetics: Elimination Half-life (t1/2z) Baseline	—	46.5 hours Interval 29.1 to 104.0	—
Pharmacokinetics: Elimination Half-life (t1/2z) Week 26	—	46.7 hours Interval 29.4 to 63.5	—

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 3, 24, 72, 168, 240 and 336 hours post-dose on Day 1 (Baseline)

Population: Analysis was performed on PK population. Here, 'overall number of participants analyzed' = participants with available data for this OM. Data for this OM was planned to be collected and analyzed for combined population of Arm A and B.

CL is defined as the rate at which the drug is removed from the body. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Baseline; however, participants did not receive BIVV001 dose in week 2 and week 27.

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=153 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Pharmacokinetics: Clearance (CL)	—	0.508 milliliter per hour per kilogram Standard Deviation 0.124	—

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 3, 24, 72, 168, 240, and 336 hours post-dose on Week 26

Population: Analysis was performed on PK population. Here, 'overall number of participants analyzed' = participants with available data for this OM. Data for this OM was planned to be collected and analyzed for combined population of Arm A and B. For Week 26, PK samples were collected and analyzed for arm A only as per protocol.

CLss is defined as the rate at which the drug is removed from the body at steady state. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Week 26; however, participants did not receive BIVV001 dose in week 2 and week 27.

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=17 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Pharmacokinetics: Total Clearance at Steady State (CLss)	—	0.449 milliliter per hour per kilogram Standard Deviation 0.101	—

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 3, 24, 72, 168, 240, and 336 hours post-dose on Week 26

Population: Analysis was performed on PK population. Here, 'overall number of participants analyzed' = participants with available data for this OM. Data for this OM was planned to be collected and analyzed for combined population of Arm A and B. For Week 26, PK samples were collected and analyzed for arm A only as per protocol.

AI is the ratio of accumulation of a drug under steady state conditions (i.e., after repeated administration) as compared to a single dose. AI was calculated as ratio of area under the curve (AUC) at Week 26 (Day 183) divided by AUC at Day 1, where AUC is the area under the plasma concentration versus time curve from time 0 to infinity. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Week 26; however, participants did not receive BIVV001 dose in week 2 and week 27.

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=15 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Pharmacokinetics: Accumulation Index (AI)	—	1.17 ratio Standard Deviation 0.160	—

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 3, 24, 72, 168, 240 and 336 hours post-dose on Day 1 (Baseline); pre-dose, 0.25, 3, 24, 72, 168, 240, and 336 hours post-dose on Week 26 (Day 183)

Population: Analysis was performed on PK population. Here, 'number analyzed' = participants with available data for each specified category. Data for this OM was planned to be collected and analyzed for combined population of Arm A and B. For Week 26, PK samples were collected and analyzed for arm A only as per protocol.

AUC0-tau was defined as area under the plasma concentration-time profile from time zero (pre-dose) to dosing interval. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Baseline and at Week 26; however, participants did not receive BIVV001 dose in week 2 and week 27.

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=159 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Pharmacokinetics: Area Under the Plasma FVIII Activity Versus Time Curve (AUC0-tau) Baseline	—	9600 hour*IU/deciliter Standard Deviation 2010	—
Pharmacokinetics: Area Under the Plasma FVIII Activity Versus Time Curve (AUC0-tau) Week 26	—	11800 hour*IU/deciliter Standard Deviation 2720	—

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 3, 24, 72, 168, 240 and 336 hours post-dose on Day 1 (Baseline); pre-dose, 0.25, 3, 24, 72, 168, 240, and 336 hours post-dose on Week 26 (Day 183)

Population: Analysis was performed on PK population. Here, 'number analyzed' = participants with available data for each specified category. Data for this OM was planned to be collected and analyzed for combined population of Arm A and B. For Week 26, PK samples were collected and analyzed for arm A only as per protocol.

Volume of distribution (Vd) is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss is the apparent volume of distribution at steady-state. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Baseline and at Week 26; however, participants did not receive BIVV001 dose in week 2 and week 27.

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=159 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Pharmacokinetics: Volume of Distribution at Steady State (Vss) Baseline	—	31.7 milliliters per kilogram Standard Deviation 7.44	—
Pharmacokinetics: Volume of Distribution at Steady State (Vss) Week 26	—	29.6 milliliters per kilogram Standard Deviation 8.26	—

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 3, 24, 72, 168, 240 and 336 hours post-dose on Day 1 (Baseline); pre-dose, 0.25, 3, 24, 72, 168, 240, and 336 hours post-dose on Week 26 (Day 183)

Population: Analysis was performed on PK population. Here, 'number analyzed' = participants with available data for each specified category. Data for this OM was planned to be collected and analyzed for combined population of Arm A and B. For Week 26, PK samples were collected and analyzed for arm A only as per protocol.

MRT is the average total time a drug molecule spends in the body. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Baseline and at Week 26; however, participants did not receive BIVV001 dose in week 2 and week 27.

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=159 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Pharmacokinetics: Mean Residence Time (MRT) Baseline	—	61.9 hours Interval 34.3 to 111.0	—
Pharmacokinetics: Mean Residence Time (MRT) Week 26	—	66.1 hours Interval 46.7 to 92.3	—

SECONDARY outcome

Timeframe: Pre-dose, 0.25 hours post-dose on Day 1 (Baseline); pre-dose, 0.25 hours post-dose on Week 26 (Day 183)

Population: Analysis was performed on PK population. Here, 'number analyzed' = participants with available data for each specified category. Data for this OM was planned to be collected and analyzed for combined population of Arm A and B. For Week 26, PK samples were collected and analyzed for arm A only as per protocol.

IR was calculated as (Peak activity [in IU/dL] - Trough activity [in IU/dL])/Actual Dose (in IU/kg), and peak activity at each visit was the highest activity level after the dosing, and trough activity at each visit was the activity level prior to the dosing.

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=159 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Pharmacokinetics: Incremental Recovery (IR) Baseline	—	2.60 IU/dL per IU/kg Standard Deviation 0.648	—
Pharmacokinetics: Incremental Recovery (IR) Week 26	—	3.05 IU/dL per IU/kg Standard Deviation 0.592	—

SECONDARY outcome

Timeframe: Pre-dose at Baseline (Day 1) and Week 52

Population: Analysis was performed on PK population. Here, 'number analyzed' = participants with available data for each specified category.

Ctrough is the pre-dose concentration of a drug.

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=133 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 n=26 Participants Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Pharmacokinetics: Trough Concentration for BIVV001 (Ctrough) Baseline	—	0.00 IU/dL Standard Deviation 0.00	0.00 IU/dL Standard Deviation 0.00
Pharmacokinetics: Trough Concentration for BIVV001 (Ctrough) Week 52	—	15.70 IU/dL Standard Deviation 10.72	21.14 IU/dL Standard Deviation 29.59

SECONDARY outcome

Timeframe: Pre-dose and 0.25, 3, 24, 72, 168, 240 and 336 hours post-dose on Day 1 (Baseline)

Population: Analysis was performed on PK population. Data for this OM was planned to be collected and analyzed for combined population of Arm A and B.

Time above predefined (10 and 40%) FVIII activity levels mean time which BIVV001 maintains above 10 IU/dL and 40 IU/dL with single dose of 50 IU/kg. Only for participants who were enrolled in sequential PK subgroup of study, PK samples were collected for all timepoints at Baseline; however, participants did not receive BIVV001 dose in week 2 and week 27.

Outcome measures

Measure	Arm B: Prophylaxis Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	Arm A: Prophylaxis n=159 Participants Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm A: BIVV001 Prophylaxis in EFC16293 Participants who received BIVV001 50 IU/kg (prophylaxis treatment regimen) for at least 6 months in current study (EFC16293) and had at least 6 months prophylaxis treatment regimen (with marketed FVIII products) in study OBS16221 prior to enrollment in the current study.
Pharmacokinetics: Time Above Predefined (10 and 40%) FVIII Activity Levels Time to 10 IU/dL	—	185 hours Interval 111.0 to 330.0	—
Pharmacokinetics: Time Above Predefined (10 and 40%) FVIII Activity Levels Time to 40 IU/dL	—	85.1 hours Interval 44.4 to 156.0	—

Adverse Events

Arm A: Prophylaxis

Serious events: 13 serious events

Other events: 56 other events

Deaths: 0 deaths

Arm B: On-demand

Serious events: 2 serious events

Other events: 7 other events

Deaths: 1 deaths

Arm B: Prophylaxis

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

BIVV001 (Efanesoctocog Alfa): All Participants

Serious events: 15 serious events

Other events: 64 other events

Deaths: 1 deaths

Serious adverse events

Measure	Arm A: Prophylaxis n=133 participants at risk Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm B: On-demand n=26 participants at risk Participants who were on an on-demand treatment regimen with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection as an on-demand treatment (as needed for the treatment of bleeding episodes) from Week 1 to Week 26 in current study.	Arm B: Prophylaxis n=26 participants at risk Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	BIVV001 (Efanesoctocog Alfa): All Participants n=159 participants at risk All participants who were enrolled in study and received BIVV001 in either Arm A or B.
Infections and infestations Covid-19 Pneumonia	0.00% 0/133 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	3.8% 1/26 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.63% 1/159 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal Cell Carcinoma	0.75% 1/133 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.63% 1/159 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic Carcinoma Metastatic	0.00% 0/133 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	3.8% 1/26 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.63% 1/159 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.
Nervous system disorders Cubital Tunnel Syndrome	0.75% 1/133 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.63% 1/159 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.
Nervous system disorders Status Epilepticus	0.75% 1/133 • Number of events 2 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.63% 1/159 • Number of events 2 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.
Nervous system disorders Ulnar Tunnel Syndrome	0.75% 1/133 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.63% 1/159 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.
Cardiac disorders Angina Pectoris	0.75% 1/133 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.63% 1/159 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.
Musculoskeletal and connective tissue disorders Arthropathy	0.75% 1/133 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.63% 1/159 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.
Musculoskeletal and connective tissue disorders Haemophilic Arthropathy	1.5% 2/133 • Number of events 2 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	1.3% 2/159 • Number of events 2 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.
Musculoskeletal and connective tissue disorders Mobility Decreased	0.75% 1/133 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.63% 1/159 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.
Investigations Blood Glucose Increased	0.75% 1/133 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.63% 1/159 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.
Investigations Cd4 Lymphocytes Decreased	0.75% 1/133 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.63% 1/159 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.
Injury, poisoning and procedural complications Combined Tibia-Fibula Fracture	0.75% 1/133 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.63% 1/159 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.
Injury, poisoning and procedural complications Traumatic Haemorrhage	0.75% 1/133 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.63% 1/159 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.
Surgical and medical procedures Central Venous Catheter Removal	0.75% 1/133 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.63% 1/159 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.
Product Issues Device Breakage	0.75% 1/133 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.63% 1/159 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.

Other adverse events

Measure	Arm A: Prophylaxis n=133 participants at risk Participants who were on a prophylaxis treatment with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection QW for 52 weeks in the current study. Study OBS16221 participants with 6 months historical data on prophylaxis treatment with a marketed FVIII product prior to enrollment were analyzed as a subgroup (named as: Arm A: Historical Prophylaxis (OBS16221) in the outcome measure analysis.	Arm B: On-demand n=26 participants at risk Participants who were on an on-demand treatment regimen with a FVIII product prior to study EFC16293 including participants who rolled over from study OBS16221, received BIVV001 50 IU/kg IV injection as an on-demand treatment (as needed for the treatment of bleeding episodes) from Week 1 to Week 26 in current study.	Arm B: Prophylaxis n=26 participants at risk Participants who received BIVV001 50 IU/kg IV injection as an on-demand treatment from Week 1 to Week 26 and were switched to prophylaxis dosing and received BIVV001 50 IU/kg, IV injection QW until Week 52 in the current study.	BIVV001 (Efanesoctocog Alfa): All Participants n=159 participants at risk All participants who were enrolled in study and received BIVV001 in either Arm A or B.
Nervous system disorders Headache	19.5% 26/133 • Number of events 40 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	19.2% 5/26 • Number of events 5 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	3.8% 1/26 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	20.1% 32/159 • Number of events 46 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.
Musculoskeletal and connective tissue disorders Arthralgia	18.8% 25/133 • Number of events 31 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	3.8% 1/26 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	16.4% 26/159 • Number of events 32 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.
Musculoskeletal and connective tissue disorders Back Pain	6.0% 8/133 • Number of events 9 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	3.8% 1/26 • Number of events 1 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	5.7% 9/159 • Number of events 10 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.
General disorders Fatigue	5.3% 7/133 • Number of events 8 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	4.4% 7/159 • Number of events 8 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.
Injury, poisoning and procedural complications Fall	7.5% 10/133 • Number of events 11 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	0.00% 0/26 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.	6.3% 10/159 • Number of events 11 • Arm A: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55); Arm B: On-demand: Baseline to Week 26 and Arm B: Prophylaxis: From Week 26 to 3 weeks post last dose of BIVV001 in Week 52 (i.e., up to Week 55); Overall arm: From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55) Reported AEs and deaths were treatment-emergent AEs that developed, worsened or became serious from Baseline (Day 1) up to 3 weeks post last dose. Analysis was performed on safety population. AE were planned to be collected and analyzed separately in Arm B for participants during on-demand and during prophylaxis and additionally analyzed and reported for all participants combined.

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