Arrowhead Pharmaceuticals’ experimental drug plozasiran produced striking results in severe hypertriglyceridemia (sHTG) — dangerously high blood fats that can trigger acute pancreatitis, a painful and sometimes life-threatening emergency.
In the Phase 3 SHASTA-3 and SHASTA-4 studies, plozasiran delivered median triglyceride reductions of 79% and 81% at 12 months, and cut acute pancreatitis events by 78% overall — and by 100% in the highest-risk patients. The data were presented as a late-breaker at the ESC Congress 2026.
How it works
Plozasiran is an RNA interference (RNAi) therapy — an injectable that “silences” the gene for APOC3, a protein that regulates how the body clears triglycerides. Turning it down lowers blood fats at their source. Arrowhead reported no new safety signals, with favorable liver, hypersensitivity and platelet profiles. Three deaths occurred among treated patients (two cardiovascular, one from a blood cancer), all attributed to pre-existing disease and assessed as unrelated to the drug.
Why it matters
Severe hypertriglyceridemia has limited treatment options, and the biggest danger — recurrent pancreatitis — can be devastating. A drug that cuts both triglycerides and pancreatitis events could be transformative for these patients. Arrowhead plans to file for US approval (a supplemental NDA) before the end of 2026. As topline Phase 3 data, full peer-reviewed results and any approval are still ahead.