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Label indication TRYNGOLZA is indicated as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS). TRYNGOLZA is an APOC-III -directed antisense oligonucleotide (ASO) indicated as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS). ( 1 ) FDA label
Also known as ISIS 678354, AKCEA-APOCIII-LRx
Olezarsen · 10 trials · 6 indications
An analysis of covariance (ANCOVA) model was performed on the log ratio of TG value at the Primary Analysis Time Point to TG value at Baseline. The estimate of the log ratio was converted back to the original scale and percent change was calculated using formula: (ratio of TG value at the Primary Analysis Time Point to TG value at Baseline - 1) × 100.
An adverse event (AE) was defined as any unfavorable and unintended sign (including a clinically-significant abnormal laboratory finding, for example), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE was considered to be related to the investigational drug product. A TEAE was defined as any AE starting on or after the first dose of the study drug.
| Arm | Type | Description |
|---|---|---|
| Cohort 1 | EXPERIMENTAL | Participants aged 12 to \<18 years will receive multiple doses of olezarsen, at a dose level that depends on body weight, once every month by subcutaneous injection for up to 1 year. All participants may continue to the optional 1-year long-term extension period with the last dose received being after 2 years of treatment. |
| Cohort 2 | EXPERIMENTAL | Participants aged 2 to \<12 years will receive multiple doses of olezarsen, at a dose level based on information obtained from Cohort 1, once every month by subcutaneous injection for up to 1 year. All participants may continue to the optional 1-year long-term extension period with the last dose received being after 2 years of treatment. |
| Olezarsen | EXPERIMENTAL | Participants who completed either ISIS 678354-CS5 (NCT05079919) or ISIS 678354-CS6 (NCT05552326) study would be enrolled to receive olezarsen, subcutaneous (SC) injection, once every 4 weeks from Week 1 through Week 153. |
| Placebo | PLACEBO_COMPARATOR | Participants will be randomized to receive olezarsen-matching placebo, once every 4 weeks by SC injection up to Week 49. |
| Olezarsen 50 mg | EXPERIMENTAL | Participants received olezarsen, 50 milligrams (mg), once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period. |
| Olezarsen 80 mg | EXPERIMENTAL | Participants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period. |
| Pooled Placebo | PLACEBO_COMPARATOR | Participants in each cohort (A, B, C and D) were randomized to receive placebo at a dose-matched volume of study drug (ISIS 678354). |
| Cohort A: ISIS 678354: 10 mg Q4W | EXPERIMENTAL | Cohort A participants received 10 milligrams (mg) ISIS 678354, subcutaneous (SC) injection, once every 4 weeks (Q4W), for up to 49 weeks and a maximum of 13 doses. |
| Cohort C: ISIS 678354: 15 mg Q2W | EXPERIMENTAL | Cohort C participants received 15 mg ISIS 678354, SC injection, once every 2 weeks (Q2W) for up to 51 weeks and a maximum of 26 doses. |
| Cohort D: ISIS 678354: 10 mg QW | EXPERIMENTAL | Cohort D participants received 10 mg ISIS 678354, SC injection, once weekly (QW) for up to 52 weeks and a maximum of 52 doses. |
| Cohort B: ISIS 678354: 50 mg Q4W | PLACEBO_COMPARATOR | Cohort B participants received 50 mg ISIS 678354, SC injection, once Q4W for up to 49 weeks and a maximum of 13 doses. |
| Name | Type | Description |
|---|---|---|
| Olezarsen | DRUG | Olezarsen will be administered by subcutaneous injection. |
| Placebo | DRUG | Olezarsen-matching placebo will be administered by SC injection. |
| ISIS 678354 | DRUG | ISIS 678354 solution for SC injection. |
Key Inclusion Criteria: 1. Parental or legally authorized representative consent must be obtained, and the participants must provide age-appropriate or cognition-appropriate assent, as determined by the Investigator. The parent or legal guardian must be able to understand and comply with the study ...
Olezarsen is an investigational RNA therapy developed by Ionis Pharmaceuticals for lowering triglyceride levels in people with familial chylomicronemia syndrome and hypertriglyceridemia, including severe hypertriglyceridemia. It is an antisense inhibitor designed to target apolipoprotein C-III (APOC3) and is being studied in Phase 3 clinical trials.
Olezarsen targets APOC3, the gene for apolipoprotein C-III. It is an antisense inhibitor, an RNA therapy that binds APOC3 RNA to reduce production of apolipoprotein C-III, a protein involved in regulating triglyceride levels in the blood. This mechanism underlies its development for familial chylomicronemia syndrome and hypertriglyceridemia.
Olezarsen is being developed by Ionis Pharmaceuticals, Inc., which trades on Nasdaq under the ticker IONS. Ionis is the sponsor of the Phase 3 clinical program evaluating olezarsen in familial chylomicronemia syndrome, hypertriglyceridemia, and severe hypertriglyceridemia.
Olezarsen is in Phase 3 clinical development. It is investigational and is being studied in placebo-controlled, randomized, double-blind trials across familial chylomicronemia syndrome, hypertriglyceridemia, and severe hypertriglyceridemia. Olezarsen has received Orphan Drug and Fast Track designations from the FDA.
Olezarsen has been studied in Phase 3 trials including NCT05610280 in hypertriglyceridemia and atherosclerotic cardiovascular disease or severe hypertriglyceridemia, and NCT05552326 in severe hypertriglyceridemia, both completed. CORE-OLE (NCT05681351) in severe hypertriglyceridemia is active but not recruiting, and NCT07727538 is recruiting pediatric participants with familial chylomicronemia syndrome.
Yes, ISIS 678354 is an alternative name for olezarsen. The Phase 3 CORE-OLE trial in severe hypertriglyceridemia and the Phase 3 trial in hypertriglyceridemia and atherosclerotic cardiovascular disease both list the study drug as olezarsen (ISIS 678354), so searches for either name refer to the same Ionis Pharmaceuticals asset.