Trial Outcomes & Findings for A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) Administered to Patients With Familial Chylomicronemia Syndrome (FCS) (NCT NCT04568434)

NCT ID: NCT04568434

Last Updated: 2025-03-06

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

66 participants

Primary outcome timeframe

Baseline, Month 6

Results posted on

2025-03-06

Participant Flow

Participants took part in the study at investigative sites in the United States, Canada, France, Italy, Netherlands, Norway, Portugal, Slovakia, Spain, Sweden and the United Kingdom from 18 November 2020 to 17 October 2023.

Participants with Familial Chylomicronemia Syndrome (FCS) were enrolled and randomized to receive either olezarsen (50 milligrams \[mg\] or 80 mg) or olezarsen-matching placebo for a 53-week treatment period. Participants completing treatment had an option to enroll in the Open-label Extension (OLE) Study ISIS 678354-CS13 (NCT05130450).

Participant milestones

Participant milestones
Measure	Placebo Participants received olezarsen-matching placebo, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 50 mg Participants received olezarsen 50 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 80 mg Participants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.
Overall Study STARTED	23	21	22
Overall Study COMPLETED	22	19	19
Overall Study NOT COMPLETED	1	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received olezarsen-matching placebo, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 50 mg Participants received olezarsen 50 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 80 mg Participants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.
Overall Study Voluntary Withdrawal	0	1	1
Overall Study Adverse Events (AE) or Serious Adverse Events (SAE)	0	1	2
Overall Study Investigator Judgement	1	0	0

Baseline Characteristics

A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) Administered to Patients With Familial Chylomicronemia Syndrome (FCS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=23 Participants Participants received olezarsen-matching placebo, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 50 mg n=21 Participants Participants received olezarsen 50 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 80 mg n=22 Participants Participants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Total n=66 Participants Total of all reporting groups
Age, Continuous	44.0 years STANDARD_DEVIATION 14.67 • n=5 Participants	43.2 years STANDARD_DEVIATION 12.11 • n=7 Participants	47.7 years STANDARD_DEVIATION 13.30 • n=5 Participants	45 years STANDARD_DEVIATION 13.38 • n=4 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	15 Participants n=7 Participants	11 Participants n=5 Participants	38 Participants n=4 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants	28 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=5 Participants	18 Participants n=7 Participants	21 Participants n=5 Participants	59 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	22 Participants n=5 Participants	17 Participants n=7 Participants	17 Participants n=5 Participants	56 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Fasting Triglycerides (TG)	2595.7 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 1255.72 • n=5 Participants	2683.8 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 1235.06 • n=7 Participants	2613.1 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 1498.96 • n=5 Participants	2629.5 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 1315.45 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Month 6

Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.

Outcome measures

Outcome measures
Measure	Placebo n=23 Participants Participants received olezarsen-matching placebo, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 50 mg n=21 Participants Participants received olezarsen 50 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 80 mg n=22 Participants Participants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.
Percent Change From Baseline in Fasting TG at Month 6	11.52 percent change Interval -5.321 to 28.356	-10.85 percent change Interval -27.797 to 6.095	-31.99 percent change Interval -49.031 to -14.94

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.

Outcome measures

Outcome measures
Measure	Placebo n=23 Participants Participants received olezarsen-matching placebo, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 50 mg n=21 Participants Participants received olezarsen 50 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 80 mg n=22 Participants Participants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.
Percent Change From Baseline in Fasting TG at Month 12	20.89 percent change Interval 1.016 to 40.764	-22.92 percent change Interval -42.505 to -3.336	-38.50 percent change Interval -58.187 to -18.815

SECONDARY outcome

Timeframe: Baseline, Months 6 and 12

Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.

Outcome measures

Outcome measures
Measure	Placebo n=23 Participants Participants received olezarsen-matching placebo, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 50 mg n=21 Participants Participants received olezarsen 50 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 80 mg n=22 Participants Participants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.
Percent Change From Baseline in Fasting Apolipoprotein C-III (apoC-III) at Months 6 and 12 Month 6	7.57 percent change Interval -5.229 to 20.359	-57.91 percent change Interval -71.193 to -44.631	-66.13 percent change Interval -79.437 to -52.823
Percent Change From Baseline in Fasting Apolipoprotein C-III (apoC-III) at Months 6 and 12 Month 12	17.08 percent change Interval 2.149 to 32.009	-59.98 percent change Interval -75.163 to -44.795	-64.20 percent change Interval -79.408 to -48.984

SECONDARY outcome

Timeframe: Month 6

Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.

Percentages are rounded off to the nearest single decimal place.

Outcome measures

Outcome measures
Measure	Placebo n=23 Participants Participants received olezarsen-matching placebo, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 50 mg n=21 Participants Participants received olezarsen 50 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 80 mg n=22 Participants Participants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.
Percentage of Participants With ≥ 40% Reduction in Fasting TG at Month 6	4.3 percentage of participants	33.3 percentage of participants	40.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Months 6 and 12

Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.

Outcome measures

Outcome measures
Measure	Placebo n=23 Participants Participants received olezarsen-matching placebo, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 50 mg n=21 Participants Participants received olezarsen 50 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 80 mg n=22 Participants Participants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.
Percent Change From Baseline in Fasting Apolipoprotein B-48 (apoB-48) at Months 6 and 12 Month 6	24.50 percent change Interval -9.972 to 58.973	-8.78 percent change Interval -42.976 to 25.406	-59.46 percent change Interval -93.164 to -25.765
Percent Change From Baseline in Fasting Apolipoprotein B-48 (apoB-48) at Months 6 and 12 Month 12	-3.52 percent change Interval -53.159 to 46.124	-36.41 percent change Interval -77.689 to 4.86	-79.15 percent change Interval -118.442 to -39.861

SECONDARY outcome

Timeframe: Baseline, Months 6 and 12

Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.

Outcome measures

Outcome measures
Measure	Placebo n=23 Participants Participants received olezarsen-matching placebo, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 50 mg n=21 Participants Participants received olezarsen 50 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 80 mg n=22 Participants Participants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.
Percent Change From Baseline in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Months 6 and 12 Month 6	5.33 percent change Interval -5.345 to 16.014	-12.35 percent change Interval -23.541 to -1.163	-18.86 percent change Interval -29.952 to -7.774
Percent Change From Baseline in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Months 6 and 12 Month 12	12.01 percent change Interval -2.48 to 26.494	-17.84 percent change Interval -32.128 to -3.545	-27.69 percent change Interval -41.722 to -13.664

SECONDARY outcome

Timeframe: During the treatment period Week 1 through Week 53

Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo. Overall number of participants analyzed is the number of participants with a history of pancreatitis within 10 years prior to screening. As prespecified in the protocol, data for this outcome measure was collected and reported in a pooled manner for olezarsen (combined Olezarsen 50 mg + Olezarsen 80 mg)

All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the Acute Pancreatitis Adjudication Committee (PAC) Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the treatment period.

Outcome measures

Outcome measures
Measure	Placebo n=15 Participants Participants received olezarsen-matching placebo, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 50 mg n=32 Participants Participants received olezarsen 50 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 80 mg Participants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.
Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During the Treatment Period (Week 1 Through Week 53) in Participants With Prior History of Pancreatitis	66.22 events per 100 participant-years Interval 30.49 to 143.817	6.73 events per 100 participant-years Interval 1.612 to 28.087	—

SECONDARY outcome

Timeframe: During the treatment period Week 1 through Week 53

Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo. As prespecified in the protocol, data for this outcome measure was collected and reported in a pooled manner for olezarsen (combined Olezarsen 50 mg + Olezarsen 80 mg).

All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the treatment period.

Outcome measures

Outcome measures
Measure	Placebo n=23 Participants Participants received olezarsen-matching placebo, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 50 mg n=43 Participants Participants received olezarsen 50 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 80 mg Participants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.
Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During the Treatment Period (Week 1 Through Week 53)	36.31 events per 100 participant-years Interval 14.7 to 89.685	4.37 events per 100 participant-years Interval 0.942 to 20.298	—

SECONDARY outcome

Timeframe: Week 13 through Week 53

All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the specified duration.

Outcome measures

Outcome measures
Measure	Placebo n=15 Participants Participants received olezarsen-matching placebo, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 50 mg n=32 Participants Participants received olezarsen 50 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 80 mg Participants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.
Adjudicated Acute Pancreatitis Mean Event Per 100 Participant-Years Rate During Week 13 Through Week 53 in Participants With Prior History of Pancreatitis	57.89 events per 100 participant-years Interval 24.469 to 136.972	8.17 events per 100 participant-years Interval 1.952 to 34.177	—

SECONDARY outcome

Timeframe: Week 13 through Week 53

All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the specified duration.

Outcome measures

Outcome measures
Measure	Placebo n=23 Participants Participants received olezarsen-matching placebo, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 50 mg n=43 Participants Participants received olezarsen 50 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 80 mg Participants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.
Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During Week 13 to Week 53	33.43 events per 100 participant-years Interval 13.25 to 84.321	5.42 events per 100 participant-years Interval 1.229 to 23.897	—

SECONDARY outcome

Timeframe: Month 6

Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.

Percentages are rounded off to the nearest single decimal place.

Outcome measures

Outcome measures
Measure	Placebo n=23 Participants Participants received olezarsen-matching placebo, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 50 mg n=21 Participants Participants received olezarsen 50 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 80 mg n=22 Participants Participants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.
Percentage of Participants With ≥ 70% Reduction in Fasting TG at Month 6	0 percentage of participants	4.8 percentage of participants	9.1 percentage of participants

SECONDARY outcome

Timeframe: Month 6

Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo. "Overall number of participants analyzed" indicates the number of participants with data available for analyses.

Percentages are rounded off to the nearest single decimal place.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Participants received olezarsen-matching placebo, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 50 mg n=20 Participants Participants received olezarsen 50 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 80 mg n=21 Participants Participants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.
Percentage of Participants With Fasting TG ≤ 880 mg/dL at Month 6	0 percentage of participants	10.0 percentage of participants	14.3 percentage of participants

SECONDARY outcome

Timeframe: During the treatment period Week 1 through Week 53

Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo. Overall number of participants analyzed is the number of participants with ≥ 2 adjudicated acute pancreatitis events in 5 years prior to enrollment. As prespecified in the protocol, data for this outcome measure was collected and reported in a pooled manner for olezarsen (combined Olezarsen 50 mg + Olezarsen 80 mg).

All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the treatment period.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants Participants received olezarsen-matching placebo, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 50 mg n=12 Participants Participants received olezarsen 50 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 80 mg Participants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.
Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During Treatment Period in Participants With ≥ 2 Events in 5 Years Prior to Enrollment	118.59 events per 100 participant-years Interval 61.226 to 229.698	16.59 events per 100 participant-years Interval 4.051 to 67.948	—

SECONDARY outcome

Timeframe: Week 13 to Week 53

Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo. Overall number of participants analyzed is the number of participants with ≥ 2 adjudicated acute pancreatitis events in 5 years prior to enrollment. As prespecified in the protocol, data for this outcome measure was collected and reported in a pooled manner for olezarsen (combined Olezarsen 50 mg + Olezarsen 80 mg).

All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the specified duration.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants Participants received olezarsen-matching placebo, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 50 mg n=12 Participants Participants received olezarsen 50 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 80 mg Participants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.
Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years From Week 13 to Week 53 in Participants With ≥ 2 Events in 5 Years Prior to Enrollment	106.91 events per 100 participant-years Interval 50.204 to 227.682	21.36 events per 100 participant-years Interval 5.233 to 87.219	—

SECONDARY outcome

Timeframe: Month 6

Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo. 'Overall number of participants analyzed' indicates the number of participants with data available for the analyses.

Percentages are rounded off to the nearest single decimal place.

Outcome measures

Outcome measures
Measure	Placebo n=22 Participants Participants received olezarsen-matching placebo, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 50 mg n=21 Participants Participants received olezarsen 50 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 80 mg n=22 Participants Participants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.
Percentage of Participants With Fasting TG ≤ 500 mg/dL at Month 6	0 percentage of participants	0 percentage of participants	13.6 percentage of participants

Adverse Events

Placebo

Serious events: 9 serious events

Other events: 19 other events

Deaths: 0 deaths

Olezarsen 50 mg

Serious events: 4 serious events

Other events: 17 other events

Deaths: 1 deaths

Olezarsen 80 mg

Serious events: 3 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Ionis Pharmaceuticals, Inc.

Phone: 760-603-2346

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=23 participants at risk Participants received olezarsen-matching placebo, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 50 mg n=21 participants at risk Participants received olezarsen 50 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.	Olezarsen 80 mg n=22 participants at risk Participants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.
Gastrointestinal disorders Gastric varices	4.3% 1/23 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/21 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/22 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.
Gastrointestinal disorders Gastric varices haemorrhage	4.3% 1/23 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/21 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/22 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.
Gastrointestinal disorders Gastritis	4.3% 1/23 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/21 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/22 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.
Gastrointestinal disorders Intestinal perforation	0.00% 0/23 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/21 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	4.5% 1/22 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.
Gastrointestinal disorders Pancreatitis	17.4% 4/23 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	4.8% 1/21 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	4.5% 1/22 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.
Gastrointestinal disorders Pancreatitis acute	13.0% 3/23 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/21 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/22 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.
Gastrointestinal disorders Pancreatitis necrotising	8.7% 2/23 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/21 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/22 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.
General disorders Sudden death	0.00% 0/23 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	4.8% 1/21 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/22 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.
Hepatobiliary disorders Cholangitis	4.3% 1/23 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/21 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/22 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.
Hepatobiliary disorders Hepatic cirrhosis	0.00% 0/23 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/21 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	4.5% 1/22 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.
Infections and infestations Cellulitis	4.3% 1/23 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/21 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/22 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.
Infections and infestations Gastroenteritis bacterial	0.00% 0/23 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	4.8% 1/21 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/22 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.
Injury, poisoning and procedural complications Intentional overdose	0.00% 0/23 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	4.8% 1/21 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/22 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.
Metabolism and nutrition disorders Hypoglycaemia	4.3% 1/23 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/21 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/22 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.
Metabolism and nutrition disorders Hyponatraemia	4.3% 1/23 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/21 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/22 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.
Metabolism and nutrition disorders Pancreatogenous diabetes	4.3% 1/23 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/21 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/22 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the oral cavity	4.3% 1/23 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/21 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.	0.00% 0/22 • From the first dose of study drug up to end of the follow-up (up to Week 66) Safety analysis set included all subjects that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.