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

August 30, 2026: Arrowhead Pharmaceuticals (NASDAQ: ARWR) presented detailed pivotal Phase 3 SHASTA-3 and SHASTA-4 data for plozasiran in adults with severe hypertriglyceridemia at ESC Congress 2026 in Munich. Both studies met the primary and all prespecified secondary endpoints: median triglycerides fell 79% and 81% at Month 12 versus baseline (p<0.0001 in both), and among patients with baseline TG ≥880 mg/dL reductions were 85% in both trials. At Month 12, 91%/93% of plozasiran patients achieved TG <500 mg/dL versus 51%/50% on placebo, and 52%/55% achieved TG <150 mg/dL versus 7.9%/2.0%.

In a prespecified pooled analysis, plozasiran reduced all acute pancreatitis events by 78% versus placebo (RR 0.22; 95% CI 0.07-0.67; p=0.008), with 4.1% absolute risk reduction and NNT 24, and reduced first AP risk (HR 0.26; 95% CI 0.09-0.78; p=0.016). In patients with TG ≥500 mg/dL and prior AP, AP event rate was reduced 91% (RR 0.09; p=0.002), with 34% absolute risk reduction and NNT 3.

Safety: TEAEs were 73% in both groups; serious TEAEs 8.3% with plozasiran vs 10% placebo. Arrowhead plans an FDA sNDA for broader sHTG by year-end 2026 and intends to use a Priority Review Voucher.