Phase 3 Data Show Plozasiran Cuts Triglycerides by Up to 81% in Severe Hypertriglyceridemia

Arrowhead Pharmaceuticals announced top-line results from its Phase 3 SHASTA-3 and SHASTA-4 studies evaluating plozasiran in patients with severe hypertriglyceridemia (sHTG), a condition marked by triglyceride levels above 500 mg/dL that raises the risk of acute pancreatitis. Both studies met their primary end point of triglyceride reduction compared with placebo, along with all prespecified secondary end points, including a statistically significant reduction in acute pancreatitis events.

Across the two studies, 25 milligrams of plozasiran administered subcutaneously once every three months produced median triglyceride reductions of 79% and 81% at 12 months, compared with a placebo reduction of roughly 27%.

“We continue to see plozasiran data as best in class with respect to safety, activity, efficacy and convenience, with dosing only four times per year, and we are more confident than ever in its promise,” said Christopher Anzalone, Ph.D., president and CEO at Arrowhead. “These compelling Phase 3 data in a broad sHTG study population that closely resembles today’s diverse patient landscape demonstrate plozasiran’s potential to dramatically change the way people are treated.”

Pancreatitis Reduction Was a Key Secondary Finding

In a preplanned pooled analysis, plozasiran was associated with statistically significant reductions in both the rate of patients experiencing at least one acute pancreatitis event and the total incidence of such events. Across the broader sHTG population studied, cumulative pancreatitis events dropped 78% compared with placebo. Among patients with triglycerides above 880 milligrams per deciliter and a prior pancreatitis history, considered the highest-risk group, plozasiran was associated with a 100% reduction in pancreatitis events.

James Hamilton, M.D., chief medical officer and head of research and development at Arrowhead, said the results build on earlier Phase 2 and Phase 3 data across multiple patient populations, including those with moderate hypertriglyceridemia, mixed hyperlipidemia and familial chylomicronemia syndrome (FCS).

“These findings highlight the potential of plozasiran as a promising therapy for patients across the spectrum of sHTG,” noted Hamilton.

Safety Profile Remained Consistent

Arrowhead reported no new safety signals, describing the treatment-emergent adverse event profile as consistent with plozasiran’s established safety record. The company noted no clinically meaningful differences in liver fat content on MRI-PDFF imaging, no meaningful adverse changes in liver enzymes, no hypersensitivity cases and no thrombocytopenia signal.

Regulatory and Presentation Plans

Plozasiran is already approved under the brand name Redemplo in the United States, European Union, China, Australia and Canada for adults with genetically confirmed or clinically diagnosed FCS, the most severe form of sHTG. Arrowhead said it plans to use data from SHASTA-3, SHASTA-4 and the earlier MUIR-3 study to pursue regulatory approval in sHTG across multiple regions, starting with a planned supplemental new drug application to the FDA before the end of 2026.

Detailed results from SHASTA-3 and SHASTA-4 are scheduled to be presented as a HOT LINE Late Breaker session at the European Society of Cardiology Congress in Munich on August 30, 2026, with Gerald Watts, M.D., presenting. Arrowhead plans to host a conference call and webcast the following day to discuss the findings.