At a Glance
- Ionis’ sNDA for olezarsen in severe hypertriglyceridemia (sHTG) accepted with PDUFA date of June 30, 2026, accelerating access to a potential first-in-class therapy.
- Olezarsen achieved 72% triglyceride reduction, 85% fewer acute pancreatitis events, and 90% of patients below 500 mg/dL risk threshold vs. placebo.
- Affects 3M US adults; current therapies fail to prevent debilitating pancreatitis, highlighting olezarsen’s Breakthrough Therapy status.
- Inhibits apoC-III production; already approved as TRYNGOLZA for FCS, with results in NEJM and AHA presentations.
Written By: Marka Sheshi, PharmD
Reviewed By: Pharmacally Editorial Team
Ionis Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has accepted a supplemental New Drug Application (sNDA) for olezarsen to treat severe hypertriglyceridemia (sHTG) under Priority Review. The PDUFA target action date is June 30, 2026, accelerating potential approval for this urgent need.
“This milestone underscores the urgent need for better options in sHTG, where current therapies fall short and leave patients at risk of acute pancreatitis,” said Brett P. Monia, Ph.D., Ionis’ CEO. Olezarsen aims to be the first treatment proven to reduce life-threatening pancreatitis attacks in this population.
Strong Phase 3 Data Drives Priority Status
The sNDA relies on results from the Phase 3 CORE (NCT05079919; n=617) and CORE2 (NCT05552326; n=446) trials, run with The TIMI Study Group. These global, double-blind, placebo-controlled studies tested 50 mg or 80 mg subcutaneous olezarsen every four weeks for 12 months in adults with triglycerides ≥500 mg/dL on standard care.
Key outcomes included:
- Up to 72% placebo-adjusted reduction in triglyceride levels.
- 85% drop in acute pancreatitis events.
- Nearly 90% of patients achieving triglycerides <500 mg/dL, below the pancreatitis risk threshold.
Findings appeared in The New England Journal of Medicine and at the American Heart Association Scientific Sessions. Olezarsen earned Breakthrough Therapy designation in November 2025; Priority Review targets six-month action for drugs offering major gains in serious conditions, versus 10 months standard.
Understanding Severe Hypertriglyceridemia and Olezarsen
sHTG affects 3 million U.S. adults, with >1 million high-risk (triglycerides ≥880 mg/dL or ≥500 mg/dL plus pancreatitis history/comorbidities). It raises acute pancreatitis risk a painful emergency causing hospitalization, organ damage, or death. Standard therapies and lifestyle changes often fail to control triglycerides consistently.
Olezarsen, an RNA-targeted therapy approved as TRYNGOLZA® for familial chylomicronemia syndrome (FCS) in the U.S. and EU, inhibits liver apoC-III production to improve triglyceride metabolism.
This advances Ionis’ pipeline in lipid disorders, potentially filling a critical gap in sHTG management.
Reference
Olezarsen sNDA accepted by the FDA for Priority Review for the treatment of severe hypertriglyceridemia (sHTG), 26 February 2026, Olezarsen sNDA accepted by the FDA for Priority Review for the treatment of severe hypertriglyceridemia (sHTG) | Ionis Pharmaceuticals, Inc.
A Study of Olezarsen (ISIS 678354) Administered to Participants with Severe Hypertriglyceridemia, ClinicalTrials.gov ID NCT05079919, https://clinicaltrials.gov/study/NCT05079919
A Study of Olezarsen Administered Subcutaneously to Participants with Severe Hypertriglyceridemia, ClinicalTrials.gov ID NCT05552326, https://clinicaltrials.gov/study/NCT05552326
Marston NA, Olezarsen for Managing Severe Hypertriglyceridemia and Pancreatitis Risk. N Engl J Med. 2026 Jan 29;394(5):429-441. Epub 2025 Nov 8. PMID: 41211918, https://doi.org/10.1056/nejmoa2512761
About Writer
Marka Sheshi | Doctor of Pharmacy
Driven by a deep commitment to clinical excellence, research integrity, and impactful medical writing. With a strong foundation in pharmacotherapy and patient safety, specializes in transforming complex scientific evidence into authoritative, publication-ready content. Passionate about advancing healthcare through precise, evidence-based communication that informs practice, strengthens research visibility, and improves patient outcomes.