The FDA has approved Tryngolza (olezarsen), a once‑monthly subcutaneous injection, to be used with diet to lower triglyceride levels and reduce the risk of acute pancreatitis in adults with severe hypertriglyceridemia. Severe hypertriglyceridemia is defined as fasting triglycerides of at least 500 mg/dL; in this population, guidelines already recommend triglyceride reduction to help prevent acute pancreatitis, a sudden inflammatory condition of the pancreas that can be serious or life‑threatening. Previously approved triglyceride‑lowering drugs had not demonstrated a reduction in pancreatitis risk, making Tryngolza the first treatment shown to lower both triglycerides and the incidence of acute pancreatitis in this setting.
Severe hypertriglyceridemia is typically managed with lifestyle and dietary measures—such as weight loss, diabetes control, regular exercise, limiting or avoiding alcohol, and adherence to a low‑fat diet—alongside medications. Normal fasting triglyceride levels are below 150 mg/dL, underscoring the degree of elevation seen in this condition. The approval of Tryngolza adds a new pharmacologic option for adults whose triglycerides remain markedly elevated despite standard measures and who are at heightened risk of pancreatitis.
The FDA’s decision is supported by two randomized, double‑blind, placebo‑controlled trials that enrolled a total of 1,061 adults with severe hypertriglyceridemia. Across both studies, participants had an average baseline triglyceride level of 1,116 mg/dL. The primary endpoint in each trial was the percent change in fasting triglyceride levels from baseline to month 6, calculated as the average of measurements taken at weeks 25 and 27, compared with placebo.
In the first trial, Tryngolza produced substantial reductions in triglycerides: mean levels fell 63% from baseline with the 50 mg dose and 72% with the 80 mg dose versus placebo. In the second trial, the average triglyceride reduction was 49% for the 50 mg dose and 55% for the 80 mg dose compared with placebo. An integrated analysis pooling data from both trials showed that the rate of acute pancreatitis was lower in the Tryngolza‑treated group than in the placebo group, supporting the indication to reduce pancreatitis risk in addition to triglyceride lowering.
The most common adverse reactions observed in patients treated with Tryngolza were injection‑site reactions and increases in liver enzymes. The prescribing information advises clinicians to consider measuring liver enzymes before starting treatment or increasing the dose and to test when clinically indicated thereafter. If liver enzyme elevations persist, dose interruption or reduction may be considered. Potential allergic reactions have also been reported, including skin redness, hives, facial swelling, chills and difficulty breathing; patients are advised to seek prompt medical attention and stop Tryngolza if such symptoms occur.
Tryngolza received both Priority Review and Breakthrough Therapy designations for this indication, reflecting the FDA’s view that it addresses an unmet need in a serious condition and offers potential clinical advantages over existing therapies. The approval was granted to Ionis Pharmaceuticals.
Subscribe to our e-Newsletters
Stay up to date with the latest news, articles, and events. Plus, get special offers
from American Pharmaceutical Review – all delivered right to your inbox!
Sign up now!