Plozasiran cut triglycerides and pancreatitis events in two phase 3 trials

A once-quarterly treatment lowered triglycerides by roughly four-fifths and was linked to substantially fewer acute pancreatitis events among adults with severe hypertriglyceridemia in two phase 3 trials. At 12 months, median triglyceride reductions from baseline were 79% in SHASTA-3 and 81% in SHASTA-4.

The global, randomized, double-blind studies enrolled 757 adults receiving standard care, assigning them 25 mg of plozasiran or placebo by injection every three months. By one year, 91% and 93% of treated participants had triglycerides below 500 mg/dL, compared with 51% and 50% in the respective placebo groups. More than half of treated participants reached levels below 150 mg/dL.

In a prespecified pooled analysis, the rate of acute pancreatitis was 78% lower with plozasiran than with placebo. This represented a 4.1 percentage-point absolute risk reduction, with 24 people needing treatment for one year to prevent one event. The benefit was larger among patients with prior pancreatitis and triglycerides of at least 500 mg/dL.

Overall adverse-event rates were 73% in both groups. Worsening blood-sugar control and diarrhea were reported more often with plozasiran, while serious events occurred in 8.3% of treated participants and 10% of those receiving placebo. Already approved for familial chylomicronemia syndrome, plozasiran will now be submitted for broader US approval, with a filing planned before the end of 2026.