Researchers from Mass General Brigham have discovered that olezarsen, a drug primarily aimed at lowering triglyceride levels, can significantly reduce the risk of acute pancreatitis in patients with severe hypertriglyceridemia. This finding emerged from two randomized, placebo-controlled trials, known as CORE-TIMI 72a and CORE2-TIMI 72b, which were recently presented at the American Heart Association Scientific Sessions and published in The New England Journal of Medicine.
Severe hypertriglyceridemia, characterized by triglyceride levels exceeding 500 mg/dL, affects approximately one in 100 individuals in the United States. This condition is particularly concerning as it heightens the risk of acute pancreatitis, an inflammatory condition of the pancreas that can lead to severe complications or even be life-threatening.
The collaborative trials, conducted by the TIMI Study Group at Mass General Brigham in partnership with Ionis Pharmaceuticals, aimed to evaluate the safety and efficacy of olezarsen in reducing triglyceride levels and the associated risk of acute pancreatitis. A total of 1,063 participants from 33 countries were enrolled, all of whom had elevated triglyceride levels and were already undergoing lipid-lowering therapy.
In the study, participants received monthly injections of olezarsen at doses of either 50 mg or 80 mg for a duration of 12 months. Results showed that over 85% of patients receiving olezarsen achieved triglyceride levels below 500 mg/dL, compared to only 35% in the placebo group.
The trials reported a total of 29 acute pancreatitis events. Notably, the incidence of acute pancreatitis in the pooled olezarsen groups was 1.1 per 100 patient years, in stark contrast to 6.2 per 100 patient years in the placebo group. This translates to an impressive 85% relative risk reduction for those treated with olezarsen.
Lead author, Nicholas Marston, MD, MPH, a cardiologist at Mass General Brigham Heart and Vascular Institute, emphasized the importance of these findings. He stated, “These findings support olezarsen’s potential to become a cornerstone therapy for severe hypertriglyceridemia, particularly for preventing a serious and potentially life-threatening condition.”
The long-term effectiveness and safety of olezarsen are currently being assessed in an ongoing open-label extension study, which will provide further insights into its role in managing severe hypertriglyceridemia and reducing the risk of acute pancreatitis.
For more detailed information, refer to the study by Nicholas A. Marston et al, titled “Olezarsen for Managing Severe Hypertriglyceridemia and Pancreatitis Risk,” published in The New England Journal of Medicine (2025). DOI: 10.1056/nejmoa2512761.