- Question
- Can plozasiran, an siRNA that reduces hepatic production of apolipoprotein C-III, lower triglycerides and the risk of acute pancreatitis in patients with persistent chylomicronemia?
- Design
- Phase 3, randomized, double-blind (quadruple masking), placebo-controlled trial of 75 patients. Participants received subcutaneous plozasiran or placebo every 3 months for 12 months.
- Population
- Adults with persistent chylomicronemia, with or without a genetic diagnosis of familial chylomicronemia syndrome. Median baseline triglycerides were 2044 mg/dL.
- Intervention
- Subcutaneous plozasiran, 25 mg or 50 mg, every 3 months for 12 months.
- Control
- Volume-matched placebo given every 3 months.
- Primary outcome
- Median percent change from baseline in fasting triglycerides at 10 months.
- Results
- At 10 months, the median change in triglycerides was -80% with 25 mg, -78% with 50 mg, and -17% with placebo (P<0.001). Key secondary end points also favored plozasiran, including the incidence of acute pancreatitis (OR 0.17; 95% CI 0.03 to 0.94; P = 0.03).
- Safety
- The risk of adverse events was similar across groups; the most common were abdominal pain, nasopharyngitis, headache, and nausea. Severe and serious adverse events were less common with plozasiran than with placebo. Hyperglycemia occurred with plozasiran in some patients with prediabetes or diabetes at baseline.
- Conclusion
- In persistent chylomicronemia, plozasiran significantly lowered triglycerides and the incidence of pancreatitis compared with placebo.
- Why it matters
- It offers a targeted apoC-III strategy for a disease with few effective treatment options and a risk of recurrent pancreatitis, and supports this pathway as a therapeutic target.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 21, 2026