Triglyceride-Lowering Drug Significantly Reduced Rate of Acute Pancreatitis in High-Risk Patients

In two placebo-controlled clinical trials, researchers at Mass General Brigham found that olezarsen benefited those with severe hypertriglyceridemia.

Researchers from Mass General Brigham have found that olezarsen—a drug designed to lower triglyceride levels—can also decrease the risk of acute pancreatitis, a potential complication in patients with severely elevated triglyceride levels. The results, from two randomized, placebo-controlled trials (CORE-TIMI 72a and CORE2-TIMI 72b), were presented at the American Heart Association Scientific Sessions and simultaneously published in The New England Journal of Medicine.

Severe hypertriglyceridemia is a condition in which the level of triglycerides (a type of fat that circulates in the blood) is very high. Approximately 1 in 100 people in the U.S. have severe hypertriglyceridemia. The condition puts people at risk for acute pancreatitis, inflammation of the pancreas that can be life-threatening.

The trials, which were designed collaboratively between the TIMI Study Group at Mass General Brigham and Ionis Pharmaceuticals, the trials’ sponsor, tested the safety and efficacy of olezarsen for reducing triglycerides and the risk of acute pancreatitis. The trials enrolled 1,063 participants across 33 countries who had fasting triglyceride levels ≥500 mg/dL and were taking lipid-lowering therapy.

“These findings support olezarsen’s potential to become a cornerstone therapy for severe hypertriglyceridemia, particularly for preventing a serious and potentially life-threating condition,” said lead author Nicholas Marston, MD, MPH, a cardiologist with the Mass General Brigham Heart and Vascular Institute. “Prevention is key in medicine, and our findings underscore the importance of clinical trials in evaluating the efficacy and safety of new treatments to improve health outcomes.”

Patients received monthly injections of olezarsen (50 mg or 80 mg) or placebo for 12 months. In 590 patients with measurements available at baseline and follow-up, more than 85% of patients taking either 50 mg or 80 mg of olezarsen saw their triglyceride levels drop below 500 mg/dL, compared with 35% in the placebo group.

There were 29 acute pancreatitis events reported across the two studies. The incidence of acute pancreatitis was 1.1 per 100 patient years in the pooled olezarsen groups, compared with 6.2 per 100 patient years in the placebo group—translating to an 85% relative risk reduction.

The long-term effectiveness and safety of olezarsen for patients with severe hypertriglyceridemia is being evaluated in an ongoing open-label extension study.

Authorship: In addition to Marston, Mass General Brigham authors include Brian A. Bergmark, Yu Mi Kang, Filipe A. Moura, Andre Zimerman, Sabina A. Murphy, Erica L. Goodrich, Shuanglu Zhang, Robert P. Giugliano, and Marc S. Sabatine. Additional authors include Veronica J. Alexander, Thomas A. Prohaska, Elaine Waldman, Julia Weinland, Shuting Xia, Dan Li, Anne C. Goldberg, Assen Goudev, Lina Badimon, Robert Gabor Kiss, Michal Vrablik, Daniel Gaudet, Philippe Moulin, Erik S.G. Stroes, Maciej Banach, Hofit Cohen, Dirk Blom, Min-Ji Charng, Børge G. Nordestgaard, Stephen J. Nicholls, and Sotirios Tsimikas.

Disclosures: The TIMI Study Group has received grant support from Ionis Pharmaceuticals for these trials. Dr. Marston has served as a consultant for Ionis Pharmaceuticals.

Funding: Both CORE-TIMI 72a and CORE2-TIMI 72b were funded by Ionis Pharmaceuticals

Paper cited: Marston NA et al. “Olezarsen for Managing Severe Hypertriglyceridemia and Pancreatitis Risk” NEJM DOI: 10.1056/NEJMoa2512761