PASADENA, Calif., July 22, 2026
Arrowhead Pharmaceuticals announced positive topline results from its pivotal Phase 3 SHASTA-3 and SHASTA-4 clinical trials, demonstrating that plozasiran achieved deep, durable, and statistically significant triglyceride reductions in patients with severe hypertriglyceridemia (sHTG). The studies successfully met their primary endpoint and all prespecified secondary endpoints, including a significant reduction in acute pancreatitis events compared with placebo. The company reported median triglyceride reductions of 79% in SHASTA-3 and 81% in SHASTA-4 after 12 months of treatment with 25 mg plozasiran administered once every three months, reinforcing the therapy’s potential to transform treatment for patients at high risk of life-threatening complications associated with elevated triglyceride levels.
Phase 3 Studies Deliver Strong Efficacy and Pancreatitis Protection
Across both global Phase 3 studies involving approximately 750 participants, plozasiran consistently demonstrated clinically meaningful improvements over placebo. In a pooled analysis, treatment significantly reduced both the number of patients experiencing acute pancreatitis (AP) and the overall incidence of AP events. Among the broader severe hypertriglyceridemia population, acute pancreatitis events were reduced by 78%, while the highest-risk subgroup—patients with triglyceride levels above 880 mg/dL and a previous history of pancreatitis—experienced an unprecedented 100% reduction in acute pancreatitis events compared with placebo. The therapy also maintained a favorable safety and tolerability profile, with no new safety signals, no hypersensitivity cases, no thrombocytopenia signal, and no clinically meaningful liver safety concerns, further supporting its long-term treatment potential.
Regulatory Plans Accelerate Following Positive Phase 3 Success
Building on these successful Phase 3 findings, Arrowhead Pharmaceuticals plans to pursue global regulatory approvals for plozasiran in severe hypertriglyceridemia. The company intends to submit a supplemental New Drug Application (sNDA) to the U.S. FDA before the end of 2026, followed by additional international regulatory submissions. Detailed clinical results from SHASTA-3 and SHASTA-4 will be presented during the prestigious HOT LINE Late Breaker Session at the European Society of Cardiology (ESC) Congress on August 30, 2026. According to company leadership, the consistent efficacy, quarterly dosing schedule, and encouraging safety profile position plozasiran as a potential best-in-class RNA interference (RNAi) therapy for patients living with severe hypertriglyceridemia.
Advertisement
Plozasiran Builds on REDEMPLO’s Commercial Success
Plozasiran, marketed as REDEMPLO® for familial chylomicronemia syndrome (FCS), is the first approved siRNA therapy studied in both genetically confirmed and clinically diagnosed FCS patients. The therapy works by silencing the APOC3 gene, reducing production of apolipoprotein C-III, a protein that slows triglyceride metabolism. This mechanism enables sustained triglyceride lowering through quarterly subcutaneous injections. Already approved in the United States, European Union, Canada, Australia, and China for FCS, plozasiran now has the potential to significantly expand its clinical impact into the much larger severe hypertriglyceridemia population. Arrowhead Pharmaceuticals believes these latest Phase 3 results represent a major advancement in RNAi-based cardiovascular medicine and could offer millions of patients a highly effective treatment option for reducing triglycerides and preventing acute pancreatitis, while supporting broader cardiovascular risk management in the future.
Source: Arrowhead Pharmaceuticals press release
