Arrowhead wins FDA `Breakthrough Status` for high triglycerides therapy

Arrowhead Pharmaceuticals said the U.S. Food and Drug Administration has granted Breakthrough Therapy designation to plozasiran for use with diet to lower triglyceride levels in adults with severe hypertriglyceridemia. The company said patients with triglycerides at or above 500 mg/dL face limited treatment options.

The designation is intended to speed development and review of drugs for serious conditions when early clinical data suggests a potential improvement over existing therapies. Arrowhead said it plans to complete the SHASTA-3, SHASTA-4, and MUIR-3 Phase 3 studies in mid-2026 and expects to file a supplemental New Drug Application by the end of 2026. Additional global filings are planned.

Severe hypertriglyceridemia is marked by triglyceride levels above 500 mg/dL. The most severe form, familial chylomicronemia syndrome, typically exceeds 880 mg/dL. The condition raises the risk of acute pancreatitis, including recurrent episodes that may require hospitalization. Risk increases with the concentration and features of triglyceride-rich lipoproteins, particularly chylomicrons. Few therapies sustainably reduce triglycerides below guideline thresholds.

SHASTA-3 and SHASTA-4 are double-blind, placebo-controlled Phase 3 trials assessing plozasiran in adults with severe hypertriglyceridemia. About 750 participants were assigned to receive four doses of 25 mg plozasiran or placebo over 12 months. The primary goal is the percent change in fasting triglycerides compared with placebo. Participants may enter an open-label extension after month 12.

MUIR-3 is a double-blind, placebo-controlled Phase 3 trial in adults with triglycerides above 150 mg/dL and below 500 mg/dL. About 1,450 participants were assigned to receive four doses of 25 mg plozasiran or placebo. The primary endpoint is the percent change in fasting triglycerides from baseline to month 12.

Plozasiran is an RNA interference drug designed to lower production of apolipoprotein C-III, a regulator of triglyceride metabolism. The therapy is approved in the United States as REDEMPLO for adults with familial chylomicronemia syndrome. Reported adverse reactions include hyperglycemia, headache, nausea, and injection-site reactions.

Arrowhead develops RNAi-based medicines aimed at silencing disease-causing genes.