Arrowhead Pharmaceuticals Presents New Long-Term Efficacy and Safety Data for Plozasiran Across a Spectrum of Hypertriglyceridemia at the American College of Cardiology’s 75th Annual Scientific Session and Expo

Key Takeaways

• 83% median triglyceride reduction in severe patients
• No acute pancreatitis events over two years
• 96% achieved TG <500 mg/dL, lowering pancreatitis risk
• Durable improvements in remnant and non‑HDL cholesterol
• Phase 3 programs aim FDA submission by end‑2026

Summary

Arrowhead Pharmaceuticals presented two‑year open‑label extension data for plozasiran at the ACC 75th session, showing an 83% median triglyceride reduction in severe hypertriglyceridemia and 96% of patients dropping below the 500 mg/dL pancreatitis threshold. No adjudicated acute pancreatitis events occurred, and atherogenic lipoproteins such as remnant cholesterol and non‑HDL cholesterol improved without new safety signals. The results extend earlier Phase 2b findings and support plozasiran’s potential as a durable therapy for a broad spectrum of hypertriglyceridemia patients. Arrowhead plans to file a supplemental NDA by the end of 2026.

Pulse Analysis

Hypertriglyceridemia, especially in its severe form, remains a therapeutic blind spot despite its clear link to acute pancreatitis and accelerated atherosclerotic cardiovascular disease. Traditional lipid‑lowering agents such as fibrates or omega‑3 fatty acids often fail to achieve guideline‑directed triglyceride thresholds, leaving clinicians with limited options. Arrowhead’s plozasiran, an RNA interference (RNAi) drug that silences the APOC3 gene, tackles the problem at its source by restoring lipoprotein lipase activity and enhancing triglyceride clearance. This mechanism positions plozasiran as a first‑in‑class solution for patients who have exhausted conventional therapies.

The two‑year open‑label extension presented at ACC 26 confirmed the durability of those mechanistic benefits. Patients with severe hypertriglyceridemia experienced a median 83% drop in triglycerides, while 96% fell below the 500 mg/dL level that defines high pancreatitis risk. Importantly, no adjudicated pancreatitis events were recorded, a safety milestone rarely seen in long‑term lipid trials. In addition to triglyceride suppression, the study reported consistent reductions in remnant cholesterol, non‑HDL cholesterol and ApoB, suggesting a broader atherogenic risk mitigation without new laboratory abnormalities.

Looking ahead, Arrowhead is advancing three global Phase 3 programs—SHASTA‑3, SHASTA‑4 and MUIR‑3—with a target supplemental NDA submission by year‑end 2026. If approved, plozasiran could capture a multi‑billion‑dollar market that includes both rare familial chylomicronemia syndrome patients and the far larger pool of individuals with severe hypertriglyceridemia. Success would also validate the TRiM™ platform’s ability to deliver liver‑focused RNAi therapeutics, potentially accelerating development pipelines for other cardiometabolic targets. Investors and clinicians alike will be watching the upcoming trial readouts for signals of commercial viability and broader clinical impact.