FDA Approves Olezarsen for Severe Hypertriglyceridemia and Pancreatitis Risk Reduction

FDA Approves Olezarsen for Severe Hypertriglyceridemia and Pancreatitis Risk Reduction

June 26, 2026 discoverhiddenusacom Health

The FDA approved olezarsen (Tryngolza) as the first and only therapy, used alongside diet, to lower triglycerides and reduce acute pancreatitis risk in adults with severe hypertriglyceridemia (sHTG), according to a manufacturer press release. Developed by Ionis Pharmaceuticals, the apolipoprotein C-III inhibitor is administered via a once-monthly autoinjector in 50 mg and 80 mg doses.

How does Olezarsen treat severe hypertriglyceridemia?

Olezarsen works as an apolipoprotein C-III inhibitor to lower dangerously high triglyceride levels. For patients with sHTG, achieving levels below 500 mg/dL is a critical threshold to lower the risk of acute pancreatitis, according to the manufacturer.

From Instagram — related to Severe Hypertriglyceridemia, Archna Bajaj

Archna Bajaj, MD, an assistant professor of clinical medicine at the University of Pennsylvania, stated in the release that patients often struggle to reach that 500 mg/dL mark despite lifestyle changes and other lipid-lowering therapies. Bajaj described the therapy as having the potential to redefine the treatment paradigm for those at risk of life-threatening pancreatitis attacks.

Did You Know? Olezarsen was granted FDA orphan drug status in February 2024 for the treatment of familial chylomicronemia syndrome, a rare form of severe hypertriglyceridemia.

What evidence supported the FDA approval?

The FDA based its decision on data from the phase 3 CORE and CORE2 trials published in The New England Journal of Medicine. These studies showed significant triglyceride reductions at the six-month mark. The 50 mg dose lowered levels by 49% to 63% compared to a placebo, while the 80 mg dose achieved reductions between 55% and 72%.

Long-term data at 12 months linked the therapy to a substantial drop in acute pancreatitis events. The 50 mg and 80 mg doses demonstrated reductions of 91% and 76%, respectively. Additionally, 86% of patients with baseline and 12-month data reached triglyceride levels below 500 mg/dL.

Expert Insight: Samantha Carter notes that the introduction of a targeted pharmacological agent may shift the management of sHTG from a primary reliance on restrictive dieting to a combined medical approach, potentially reducing the psychological burden and physical risk for patients who previously had no approved drug options.

What are the risks and side effects?

Clinical data identified specific adverse events associated with the therapy. According to the manufacturer, the most common side effects for patients with sHTG included increases in liver enzymes and reactions at the injection site.

What happens next for sHTG patients?

The availability of Tryngolza could provide a new clinical option for patients who previously faced a constant fear of sudden pancreatitis attacks, according to Emily Draud, interim executive director of the National Pancreas Foundation.

Because it is the only approved therapy of its kind, clinicians may now be able to combine this medication with dietary restrictions to manage triglyceride levels more aggressively. This shift could lead to a decrease in the frequency of debilitating pancreatitis events across the sHTG patient population.

Frequently Asked Questions

What is Olezarsen (Tryngolza) used for?
It is the first FDA-approved therapy indicated to lower triglycerides and reduce the risk of acute pancreatitis in adults with severe hypertriglyceridemia, used in conjunction with diet.

How is the medication administered?
The drug is an apolipoprotein C-III inhibitor administered once monthly via an autoinjector in either a 50 mg or 80 mg dose.

What were the results of the CORE and CORE2 trials?
At 12 months, the 50 mg dose reduced acute pancreatitis events by 91% and the 80 mg dose reduced them by 76%. Furthermore, 86% of patients achieved triglyceride levels below 500 mg/dL.

How do you think new targeted therapies will change the way rare metabolic conditions are managed?