Arrowhead Pharmaceuticals, Inc. presented final data from the double-blind treatment period of its Phase 2 SHASTA-2 study of investigational plozasiran (formerly ARO-APOC3) in patients with severe hypertriglyceridemia (SHTG). Results from the SHASTA-2 study showed dramatic, consistent, and sustained reductions in Apolipoprotein C-III (APOC3) and triglycerides and improvement in multiple atherogenic lipoprotein levels. These data were presented in a late-breaking oral presentation today at the American College of Cardiology 73rd Annual Scientific Session & Expo (ACC.24) in Atlanta and simultaneously published in the journal JAMA Cardiology.

Treatment with plozasiran led to dose-dependent placebo-adjusted reductions in triglycerides (primary endpoint) of -49% (P < 0.001), -53% (P < 0.001), and -57% (P < 0.001), driven by placebo-adjusted reductions in APOC3 of -68% (P < 0.001), -72% (P < 0.001), and -77% (P < 0.001) at week 24, after receiving two doses of 10 mg, 25 mg, and 50 mg plozasiran, respectively. Mean maximum, non-placebo adjusted reductions from baseline in triglycerides and APOC3 were up to 86% and 90% and typically occurred around week 16 or week 20. Significant and durable triglyceride and APOC3 reductions persisted to week 48, 36 weeks after the last dose.

There was limited interpatient variability in pharmacodynamic response across all plozasiran treatment groups. Among patients treated with plozasiran, 90.6% achieved a triglyceride level less than 500 mg/dL, the level associated with increased risk of acute pancreatitis, at week 24. In addition, 48.4% of patients achieved normal triglyceride levels of less than 150 mg/dL at week 24.