Arrowhead Pharmaceuticals plans to submit a supplemental New Drug Application to the U.S. Food and Drug Administration for plozasiran by the end of 2026, seeking approval to treat severe hypertriglyceridemia.
The filing follows positive results from two phase 3 trials, SHASTA-3 and SHASTA-4, which enrolled 757 patients receiving either 25 mg of plozasiran or a placebo subcutaneously every three months. In SHASTA-3, plozasiran reduced triglycerides by 79% compared with placebo, while SHASTA-4 showed an 81% reduction.
At the 12-month mark, more than 90% of patients treated with plozasiran achieved triglyceride levels below 500 mg/dL, compared with roughly 50% in the placebo group. Over half of the plozasiran-treated patients reached levels below 150 mg/dL, a clinically significant threshold for reducing pancreatitis risk.
A pooled analysis indicated that plozasiran reduced acute pancreatitis events by 78% versus placebo. Among high-risk patients with triglycerides at or above 500 mg/dL and a prior history of acute pancreatitis, the treatment cut event rates by 91%.
Safety data showed treatment-emergent adverse events in 73% of both plozasiran and placebo groups. Serious adverse events occurred in 8.3% of plozasiran-treated patients and 10% of placebo recipients. The most common adverse events in the plozasiran group were worsening glycemic control (14.3%) and diarrhea (5.6%). Three fatal events were reported in the plozasiran group, all attributed to pre-existing conditions and deemed unrelated to treatment.
Plozasiran is already approved as REDEMPLO for familial chylomicronemia syndrome in the U.S., Canada, China, Australia, and the European Union. Arrowhead acquired a priority review voucher for the upcoming FDA submission on August 4, 2026.
