FDA Approves TRYNGOLZA (Olezarsen) to Reduce Triglycerides and Acute Pancreatitis Risk in Severe Hypertriglyceridemia

The U.S. Food and Drug Administration (FDA) has approved TRYNGOLZA® (olezarsen) as an adjunct to diet to reduce triglyceride (TG) levels and the risk of acute pancreatitis in adults with severe hypertriglyceridemia (sHTG), defined as fasting triglyceride levels of 500 mg/dL or higher. The approval makes TRYNGOLZA the first and only therapy specifically indicated to reduce acute pancreatitis risk in this patient population. Ionis Pharmaceuticals expects the drug to become available in the United States in July 2026.

TRYNGOLZA is administered once monthly using a prefilled autoinjector and is available in 50 mg and 80 mg doses. The approval expands Ionis’ commercial portfolio beyond rare diseases and represents the company’s first independent launch in a more prevalent metabolic disorder.

Addressing a High-Risk Unmet Need

Severe hypertriglyceridemia is associated with a substantially increased risk of acute pancreatitis, a serious inflammatory condition that often requires hospitalization and may result in permanent organ damage or death. Although lifestyle modification and conventional lipid-lowering therapies remain standard care, many patients fail to reduce triglyceride levels below the clinically important threshold of 500 mg/dL, leaving them vulnerable to recurrent pancreatitis.

Olezarsen is an antisense oligonucleotide that inhibits the production of apolipoprotein C-III (ApoC-III), a key regulator of triglyceride metabolism. Lowering ApoC-III enhances triglyceride clearance from the bloodstream, resulting in sustained reductions in circulating triglyceride levels.

 Phase 3 CORE and CORE2 Results

The FDA based its approval on positive results from the Phase 3 CORE (NCT05079919) and CORE2 trials (NCT05552326), with findings published in The New England Journal of Medicine.

Across both studies, TRYNGOLZA reduced fasting triglyceride levels by up to 72% compared with placebo at six months, with reductions maintained through 12 months. The therapy also reduced acute pancreatitis events by up to 91%, demonstrating clinically meaningful protection against one of the most serious complications of severe hypertriglyceridemia.

Among patients with baseline and 12-month follow-up data, 86% achieved triglyceride levels below 500 mg/dL, a recognized target associated with lower pancreatitis risk.

The studies also reported favorable number-needed-to-treat (NNT) values. Treating 20 patients for one year prevented one episode of acute pancreatitis in the overall study population, while only four patients required treatment to prevent one event among those with baseline triglycerides of 880 mg/dL or higher and a previous history of acute pancreatitis.

TRYNGOLZA demonstrated a favorable safety profile throughout the clinical program. The most common adverse reactions occurring at least 2% more frequently than placebo were injection-site reactions and elevated liver enzymes.

Clinical and Strategic Significance

Ionis Chief Executive Officer Brett P. Monia, Ph.D., said the approval provides the first treatment that not only substantially lowers triglycerides but also reduces acute pancreatitis events in patients with severe hypertriglyceridemia. He added that the launch marks an important commercial milestone as the company’s first independently marketed therapy for a prevalent disease.

Commenting on the approval, Archna Bajaj, M.D., of the University of Pennsylvania noted that many patients remain at high risk of acute pancreatitis despite current lipid-lowering therapies and lifestyle interventions. She said the Phase 3 results position TRYNGOLZA as a therapy with the potential to reshape the treatment approach for severe hypertriglyceridemia.

Commercial Launch

Ionis will support eligible patients through its Ionis Every Step™ assistance program, which provides insurance navigation, financial support, nutrition resources, and injection training. Commercial availability of TRYNGOLZA in the United States is expected to begin in July 2026.

Reference

TRYNGOLZA® (olezarsen) approved by the FDA as the first and only treatment to reduce triglycerides and the risk of acute pancreatitis in patients with severe hypertriglyceridemia (sHTG) | Ionis Pharmaceuticals, Inc.