Arrowhead Reports Phase 3 Plozasiran Data Reducing Pancreatitis

Pasadena, Calif. – August 30, 2026

Arrowhead Links Plozasiran to Reduced Acute Pancreatitis Risk

The most important development from SHASTA-3 and SHASTA-4 is the observed reduction in acute pancreatitis events, a major complication associated with severe hypertriglyceridemia. In the prespecified pooled analysis, plozasiran reduced all AP events by 78% versus placebo, corresponding to a relative risk of 0.22, a 4.1% absolute risk reduction and a number needed to treat of 24 over one year. Plozasiran also significantly reduced the risk of a first AP event, with a hazard ratio of 0.26. The benefit became more pronounced in patients with greater baseline risk. Among patients with triglycerides of at least 500 mg/dL and a prior history of pancreatitis, the treatment reduced AP event rates by 91% versus placebo, corresponding to a reported 34% absolute risk reduction and an NNT of three over one year. In the highest-risk subgroup with triglycerides above 880 mg/dL and previous AP, Arrowhead reported a 100% reduction in events versus placebo.

Plozasiran Delivers Deep Triglyceride Lowering in Phase 3

Across both pivotal studies, plozasiran 25 mg administered once every three months produced substantial reductions in triglycerides through Month 12. Median triglyceride levels declined by 79% in SHASTA-3 and 81% in SHASTA-4, with both results achieving p<0.0001. Among patients starting with triglycerides of at least 880 mg/dL, median reductions reached 85% in both trials. At Month 12, 91% of treated patients in SHASTA-3 and 93% in SHASTA-4 had triglycerides below 500 mg/dL, compared with 51% and 50% of placebo recipients, respectively. More than half of treated patients also achieved triglycerides below 150 mg/dL. Plozasiran additionally reduced APOC3, remnant cholesterol and non-HDL cholesterol, supporting the therapeutic rationale of sustained APOC3 suppression. The results are particularly relevant to patients with sHTG because persistently elevated triglycerides can increase the risk of recurrent pancreatitis and remain difficult to control with existing treatment approaches.

Arrowhead Prepares sNDA Filing for Broader sHTG Use

The safety and tolerability profile of plozasiran remained favorable across SHASTA-3 and SHASTA-4, with treatment-emergent adverse events reported in 73% of both pooled treatment groups. Serious adverse events occurred in 8.3% of plozasiran-treated patients compared with 10% for placebo, while discontinuations because of treatment-emergent adverse events were uncommon. Arrowhead plans to use data from SHASTA-3, SHASTA-4 and MUIR-3 to pursue marketing authorization for plozasiran in the broader sHTG population across multiple geographies. The company intends to submit a supplemental New Drug Application (sNDA) to the U.S. FDA by the end of 2026 and plans to utilize an FDA Priority Review Voucher to potentially accelerate the review. Plozasiran is already approved in several regions for familial chylomicronemia syndrome under the name REDEMPLO®, making the broader sHTG application an important next regulatory step for Arrowhead’s RNAi-based lipid-lowering program.

Source: Arrowhead Pharmaceuticals press relese