Ionis Pharmaceuticals has received U.S. Food and Drug Administration (FDA) approval for TRYNGOLZA (olezarsen), a first-of-its-kind therapy designed to reduce triglyceride levels and lower the risk of acute pancreatitis in adults with severe hypertriglyceridemia (sHTG). The approval provides a new treatment option for patients living with the serious condition, which is characterized by triglyceride levels of 500 mg/dL or higher and carries a significant risk of painful and potentially life-threatening pancreatitis.
TRYNGOLZA is approved as an adjunct to diet and is available in 50 mg and 80 mg doses, administered once a month using a self-injection autoinjector. According to Ionis, it is the only FDA-approved therapy specifically indicated for severe hypertriglyceridemia that has demonstrated both substantial triglyceride reduction and a significant decrease in acute pancreatitis events.
Severe hypertriglyceridemia affects thousands of patients who often struggle to bring triglyceride levels under control despite lifestyle changes and existing lipid-lowering medications. Persistently elevated triglycerides increase the likelihood of acute pancreatitis, a serious inflammatory condition that causes severe abdominal pain, frequently requires hospitalization, and can lead to permanent organ damage or even death.
Ionis Chief Executive Officer Brett P. Monia described the approval as a landmark achievement for both patients and the company. He said TRYNGOLZA offers a long-awaited treatment capable of dramatically lowering dangerously high triglyceride levels while significantly reducing episodes of acute pancreatitis. Monia also noted that the approval marks Ionis’ first independent commercial launch in a more prevalent disease area, building on the company’s earlier success in treating familial chylomicronemia syndrome, a rare genetic form of severe hypertriglyceridemia.
The FDA’s decision was supported by positive results from the Phase 3 CORE and CORE2 clinical trials, which were published in The New England Journal of Medicine. Across both studies, patients receiving TRYNGOLZA experienced rapid and sustained reductions in fasting triglyceride levels.
Clinical data showed that the therapy lowered triglycerides by up to 72% compared with placebo after six months, with the reductions maintained through one year of treatment. In addition, TRYNGOLZA reduced acute pancreatitis events by up to 91%, highlighting its potential to address one of the most dangerous complications associated with severe hypertriglyceridemia.
Among patients who completed both baseline and 12-month evaluations, 86% achieved triglyceride levels below 500 mg/dL, the threshold widely recognized as important for reducing the risk of pancreatitis. The studies also demonstrated a favorable number needed to treat (NNT), with 20 patients requiring treatment for one year to prevent one pancreatitis episode in the overall study population. In the highest-risk subgroup—patients with triglyceride levels of 880 mg/dL or higher and a previous history of acute pancreatitis—the NNT was just four, indicating a particularly strong benefit for patients at greatest risk.
Dr. Archna Bajaj, Assistant Professor of Clinical Medicine at the University of Pennsylvania, said patients with severe hypertriglyceridemia have historically faced significant challenges in lowering triglyceride levels despite available therapies and lifestyle modifications. She noted that the clinical outcomes achieved with TRYNGOLZA have the potential to redefine treatment for the disease by offering meaningful reductions in triglycerides and the risk of pancreatitis.
The therapy also demonstrated a favorable safety and tolerability profile throughout its clinical development program. The most commonly reported side effects occurring more frequently than placebo included injection site reactions and elevated liver enzyme levels, with no unexpected safety concerns identified.
Patient advocacy groups also welcomed the approval. Emily Draud, Interim Executive Director of the National Pancreas Foundation, said many people living with severe hypertriglyceridemia face constant uncertainty because acute pancreatitis attacks can occur without warning. She described the availability of TRYNGOLZA as an important advance that offers new hope for reducing the risk of these potentially life-threatening events while highlighting the continued need for innovation in pancreatic disease care.
To support patients beginning treatment, Ionis announced that it will provide comprehensive assistance through its Ionis Every Step™ program. The service includes insurance and reimbursement support, financial assistance for eligible patients, injection training, and educational resources, including nutritional guidance, to help improve treatment adherence and patient outcomes.
With the FDA approval of TRYNGOLZA, Ionis expands its commercial portfolio and introduces a therapy that could significantly change the standard of care for adults living with severe hypertriglyceridemia who remain at high risk of acute pancreatitis.