Arrowhead announces new Phase 2 SHASTA-2 study of plozasiran in SHTG

Arrowhead Pharmaceuticals presented final data from the double-blind treatment period of its Phase 2 SHASTA-2 study of investigational plozasiran in patients with severe hypertriglyceridemia, or SHTG. Results from the SHASTA-2 study showed dramatic, consistent, and sustained reductions in Apolipoprotein C-III and triglycerides and improvement in multiple atherogenic lipoprotein levels. Treatment with plozasiran led to dose-dependent placebo-adjusted reductions in triglycerides of -49%, -53%, and -57%, driven by placebo-adjusted reductions in APOC3 of -68%, -72%, and -77% 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. Subjects treated with plozasiran also showed improvements in multiple atherogenic lipid and lipoprotein levels, including remnant cholesterol, HDL-cholesterol, and non-HDL cholesterol. Plozasiran demonstrated a favorable safety profile in the SHASTA-2 study. The adverse event and serious adverse event profile were similar across treatment groups. Observed adverse events generally reflected the comorbidities and underlying conditions of the study population. All serious treatment emergent adverse events were deemed not related to plozasiran.