FDA approves first drug to reduce pancreatitis risk in severe hypertriglyceridemia

FDA has approved Tryngolza (olezarsen) as an adjunct to diet to reduce triglycerides and the risk of acute pancreatitis in adults with severe hypertriglyceridemia.

Severe hypertriglyceridemia, defined as fasting triglycerides of at least 500 mg/dL, can lead to acute pancreatitis, a potentially life-threatening complication. Although existing therapies can lower triglycerides, FDA noted that previously approved triglyceride-lowering drugs had not shown a reduced risk of acute pancreatitis in trials with enough pancreatitis events to assess that outcome.

Tryngolza is an RNA-targeted therapy designed to reduce production of apolipoprotein C-III, a liver-derived protein involved in triglyceride metabolism. It is given as a once-monthly subcutaneous injection and will be available in 50 mg and 80 mg doses.

FDA based the approval on CORE and CORE2, two randomized, double-blind, placebo-controlled phase 3 trials that included 1,061 adults with severe hypertriglyceridemia. Across the trials, mean baseline triglyceride level was 1,116 mg/dL.

At six months, Tryngolza reduced fasting triglycerides by 49% to 63% with the 50 mg dose and 55% to 72% with the 80 mg dose compared with placebo. In the integrated analysis, acute pancreatitis events were lower with pooled Tryngolza treatment than with placebo. The manufacturer reported pancreatitis event reductions of 91% with the 50 mg dose and 76% with the 80 mg dose at 12 months, with an 85% pooled reduction.

Ionis also reported that 86% of treated patients with baseline and 12-month data achieved triglyceride levels below 500 mg/dL, a key threshold for pancreatitis risk reduction.

The most common adverse reactions in patients with severe hypertriglyceridemia were injection-site reactions and increased liver enzymes. Clinicians should consider liver enzyme testing before starting Tryngolza or increasing the dose and when clinically indicated thereafter. Persistent liver enzyme elevations may warrant dose interruption or reduction.

Hypersensitivity reactions, including diffuse erythema, facial swelling, urticaria, chills, bronchospasm, and myalgias, have also been reported. Patients should be counseled to stop the medication and seek prompt medical attention if symptoms of hypersensitivity occur.

Tryngolza received Priority Review and Breakthrough Therapy designations for this indication. The company said the drug is expected to be available in the US in July.

“As a physician, I have seen firsthand how challenging it can be for patients with sHTG to lower their triglycerides below 500 mg/dL, despite background lipid-lowering therapies and lifestyle changes, which leaves them at risk of a devastating and potentially life-threatening acute pancreatitis attack,” said Archna Bajaj, MD, assistant professor of clinical medicine at the University of Pennsylvania. “Tryngolza is a transformational new therapy that showed unprecedented, clinically meaningful outcomes for sHTG, with the potential to redefine the treatment paradigm.”

Sources: Ionis Pharmaceuticals. 2026 June 24. [Press release]. Tryngolza (olezarsen) approved by FDA as the first and only treatment to reduce triglycerides and the risk of acute pancreatitis in patients with severe hypertriglyceridemia; US Food and Drug Administration. 2026 June 24. [News release]. FDA approves first treatment shown to reduce the risk of acute pancreatitis in adults with severe hypertriglyceridemia