Plozasiran Reduces Triglycerides and Pancreatitis Risk in Persistent Chylomicronemia Patients: NEJM

A new study published in the New England Journal of Medicine highlighted the effectiveness of plozasiran, a small interfering RNA, in managing persistent chylomicronemia which is associated with recurrent acute pancreatitis and elevated triglycerides. The phase 3 trial investigated the efficacy of plozasiran in lowering triglycerides and reducing the incidence of acute pancreatitis which yielding promising results for patients with this condition.

75 patients with persistent chylomicronemia were randomly assigned to receive either 25 mg or 50 mg of plozasiran or a placebo. This was administered subcutaneously every 3 months over 12 months with the primary goal to assess the median percentage change in fasting triglyceride levels at the 10-month mark. Secondary goals included measuring fasting triglyceride and apolipoprotein C-III level changes at 10 and 12 months, along with tracking the incidence of acute pancreatitis.

The result found significant reduction in fasting triglyceride levels in patients treated with plozasiran when compared to the placebo group. At baseline, the participants had a median triglyceride level of 2044 mg per deciliter. After 10 months, the group receiving 25 mg of plozasiran saw an 80% median reduction in triglyceride levels, while the 50 mg group underwent a 78% reduction. The participants in the placebo group saw only a 17% decrease.

The secondary outcomes further brought out the benefits of plozasiran. The occurrence of acute pancreatitis was lower in patients treated with plozasiran. The individuals who were receiving the drug had a reduced odds ratio (0.17) that indicated an 83% lower chance of developing pancreatitis when compared to the placebo group.

Adverse events, such as abdominal pain, nasopharyngitis, headache, and nausea, were reported with similar frequency across all groups. However, severe and serious adverse events were less common in the plozasiran-treated patients when compared to the individuals who were receiving placebo. Hyperglycemia was observed in some patients with pre-existing diabetes or prediabetes by indicating that careful monitoring may be necessary for certain patient groups.

Overall, this phase 3 trial demonstrated that plozasiran offers a significant benefit in managing persistent chylomicronemia, with marked reductions in triglyceride levels and a lower incidence of acute pancreatitis. While the treatment was generally well-tolerated, ongoing monitoring for hyperglycemia in certain populations is highly imperative.

Source:

Watts, G. F., Rosenson, R. S., Hegele, R. A., Goldberg, I. J., Gallo, A., Mertens, A., Baass, A., Zhou, R., Muhsin, M., Hellawell, J., Leeper, N. J., & Gaudet, D. (2024). Plozasiran for Managing Persistent Chylomicronemia and Pancreatitis Risk. In New England Journal of Medicine. Massachusetts Medical Society. https://doi.org/10.1056/nejmoa2409368