Arrowhead Presents Long-Term Data on Plozasiran for Hypertriglyceridemia

New 2-year data shows dramatic reductions in triglycerides and lack of acute pancreatitis events with investigational APOC3-targeting therapy.

Mar. 28, 2026 at 2:33pm

Got story updates? Submit your updates here. ›

Arrowhead Pharmaceuticals presented new long-term data on its investigational RNA interference therapy plozasiran, which demonstrated dramatic and durable reductions in triglyceride levels across a spectrum of hypertriglyceridemia patients over a 2-year open-label extension study. The data, presented at the American College of Cardiology's annual meeting, showed a favorable safety profile with no acute pancreatitis events, supporting plozasiran's potential as a treatment for severe hypertriglyceridemia.

Why it matters

Severe hypertriglyceridemia significantly increases the risk of acute pancreatitis, a life-threatening condition, as well as cardiovascular disease. Current treatment options are limited, so new therapies that can safely and effectively lower triglycerides are critically needed. The long-term data on plozasiran's ability to dramatically reduce triglycerides without safety concerns suggests it could become an important new tool for managing this high-risk patient population.

The details

In the 2-year open-label extension study, patients with severe hypertriglyceridemia saw a median 83% reduction in triglycerides, with 96% achieving levels below 500 mg/dL, a threshold associated with increased pancreatitis risk. Patients with moderate hypertriglyceridemia had a 67% median triglyceride reduction, with 93% reaching the 150 mg/dL target. Importantly, there were no adjudicated acute pancreatitis events in any patient receiving plozasiran during the study. The therapy also demonstrated favorable effects on other atherogenic lipoproteins like remnant cholesterol and non-HDL cholesterol.

  • The 2-year open-label extension study followed earlier positive Phase 2b studies of plozasiran in 2024 and 2025.
  • Arrowhead plans to complete the Phase 3 SHASTA-3, SHASTA-4, and MUIR-3 trials in mid-2026 and submit a supplemental NDA to the FDA by the end of 2026.

The players

Arrowhead Pharmaceuticals

A commercial-stage pharmaceutical company developing RNA interference (RNAi) therapeutics, including plozasiran, an investigational therapy targeting apolipoprotein C-III to reduce triglycerides.

Dr. Christie M. Ballantyne

Professor at Baylor College of Medicine, member of the Texas Heart Institute, and Principal Investigator of the 2-year plozasiran open-label extension study.

Christopher Anzalone, Ph.D.

President and CEO of Arrowhead Pharmaceuticals.

Got photos? Submit your photos here. ›

What they’re saying

“With a new therapy, it is always important to see longer term data to better understand both efficacy and safety. In a long-term open-label extension study, plozasiran treatment was associated with dramatic and meaningful reductions in TGs. In addition, the lack of any acute pancreatitis events during two years of treatment in a patient population that includes those at high risk was particularly reassuring.”

— Dr. Christie M. Ballantyne, Professor at Baylor College of Medicine, member of the Texas Heart Institute, and Principal Investigator of the 2-year plozasiran open-label extension study

“We're pleased with the consistent, positive clinical results we're seeing with plozasiran across the spectrum of hypertriglyceridemias and we're excited about what this could mean for patients. In the four months since its FDA approval for treating FCS, plozasiran is already making a meaningful difference for the FCS community, and we believe it has the potential to become an important therapy for people living with severe hypertriglyceridemia as well.”

— Christopher Anzalone, Ph.D., President and CEO of Arrowhead Pharmaceuticals

What’s next

Arrowhead plans to complete the Phase 3 SHASTA-3, SHASTA-4, and MUIR-3 trials in mid-2026 and submit a supplemental NDA to the FDA by the end of 2026 for approval of plozasiran to treat severe hypertriglyceridemia.

The takeaway

The long-term data on plozasiran's ability to dramatically and safely lower triglycerides across a spectrum of hypertriglyceridemia patients is highly promising, as it could provide a much-needed new treatment option for this high-risk patient population that currently has limited therapeutic choices.