Plozasiran (ARO-APOC3-3004) - (SHASTA-4)

July 22, 2026: Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) reported topline Phase 3 results from the global, double-blind, placebo-controlled SHASTA-3 (NCT06347003) and SHASTA-4 (NCT06347016) trials of plozasiran in adults with severe hypertriglyceridemia (sHTG). Both studies met the primary endpoint (percent change in fasting serum triglycerides at month 12 vs placebo) and all prespecified secondary endpoints, including a statistically significant reduction in acute pancreatitis (AP) versus placebo.

Efficacy: 25 mg plozasiran given subcutaneously once every three months produced median triglyceride reductions of 79% (SHASTA-3) and 81% (SHASTA-4) at month 12 vs ~27% with placebo. In a pre-planned pooled AP analysis, plozasiran reduced the proportion of patients with ≥1 AP event (p<0.0221) and total AP event incidence (p<0.0077). Cumulative AP events were reduced 78% in the broad sHTG population; in a highest-risk subgroup (TG >880 mg/dL plus prior AP), AP events were reduced 100% vs placebo.

Safety: No new safety signals; no hypersensitivity or thrombocytopenia signal; no meaningful liver fat or liver enzyme differences vs placebo in a prespecified subgroup.

Next catalysts: Detailed data to be presented as a HOT LINE late breaker at ESC Congress (Munich) on Aug. 30, 2026, with a company call/webcast Aug. 31, 2026. Arrowhead plans a U.S. FDA supplemental NDA for sHTG before end of 2026 and additional global submissions thereafter.