In patients with severe hypertriglyceridemia, plozasiran, a small interfering RNA that targets APOC3 messenger RNA, reduced triglyceride levels and risk of acute pancreatitis. Full results of the phase 3 SHASTA-3 and SHASTA-4 trials and Research Summary: nej.md/4iv82y3
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Nov 10, 2026 · 8:00 PM UTC

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Severe hypertriglyceridemia is one of those problems where the lab number scares you and the patient feels fine until they don't. Cutting pancreatitis risk is the outcome that actually matters here, not just the triglyceride number. I will be watching how this holds up outside the trial setting, especially on cost and access. A twice a year injection changes the conversation if patients can actually get it.
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Plozasiran already has an FDA approval (Redemplo, Nov 2025) for familial chylomicronemia, based on PALISADE (Watts et al., NEJM 2024): median triglycerides down 80% at 10 months vs 17% on placebo, with fewer pancreatitis events. SHASTA-3/4 cover the larger severe-HTG group.
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