A new study found that plozasiran may reduce triglyceride levels by up to 80% in patients with persistent chylomicronemia, lowering their risk of acute pancreatitis.
In the phase III PALISADE trial, published in The New England Journal of Medicine, researchers evaluated the efficacy of plozasiran, a hepatically targeted small interfering ribonucleic acid (RNA), in reducing triglyceride levels and the risk of acute pancreatitis in patients with persistent chylomicronemia. The condition, which includes familial chylomicronemia syndrome and multifactorial causes, is characterized by severe hypertriglyceridemia and an elevated risk of recurrent acute pancreatitis.
In the trial, 75 patients were randomly assigned to receive subcutaneous plozasiran (25 mg or 50 mg) or placebo every 3 months for 12 months. The primary endpoint of the trial was the median percentage change in fasting triglyceride levels at 10 months. The study results showed an 80% reduction in triglyceride levels in the 25 mg plozasiran group and a 78% reduction in the 50 mg group compared with a 17% reduction in the placebo group (P < .001).
Secondary endpoints, including fasting apolipoprotein C-III levels and the incidence of acute pancreatitis, also favored plozasiran. At 10 months, fasting apolipoprotein C-III levels decreased by 93% in the 25 mg plozasiran group and by 96% in the 50 mg group, whereas the placebo group had a minimal change of –1%. The incidence of pancreatitis was lower in the plozasiran groups (odds ratio = 0.17, 95% confidence interval = 0.03–0.94, P = .03).
Adverse events occurred at similar rates across all groups. Common adverse events included abdominal pain, nasopharyngitis, and headache. Hyperglycemia was observed in some patients with baseline prediabetes or diabetes who received plozasiran. Severe and serious adverse events were less frequent in the treatment groups compared with placebo.
Full disclosures can be found in the published study.