Arrowhead Pharmaceuticals (NASDAQ: ARWR) presented Sunday August 30, 2026 the full Phase 3 SHASTA-3 and SHASTA-4 12-month data of plozasiran (an RNAi therapeutic targeting APOC3, administered as quarterly subcutaneous injection) in adults with severe hypertriglyceridemia at the European Society of Cardiology Congress 2026 in Munich, Germany, in a Hot Line Late-Breaking Science session. SHASTA-3 and SHASTA-4 met their primary and all prespecified secondary endpoints with median triglyceride reductions from baseline of 79% and 81%, respectively, at Month 12 (p<0.0001 in both studies). More than 90% of plozasiran-treated patients achieved triglycerides below 500 mg/dL at Month 12, and more than half achieved TG below 150 mg/dL. In a prespecified pooled analysis, plozasiran significantly reduced acute pancreatitis events across the broad sHTG study population, with greater absolute benefit among higher-AP-risk patients. Three fatal events in the plozasiran arm (two cardiovascular deaths, one CMML death) were assessed as unrelated to study treatment. Arrowhead plans to file a supplemental NDA before end of 2026 for the broader sHTG population, building on the earlier familial chylomicronemia syndrome approval.
Alnylam Pharmaceuticals (NASDAQ: ALNY) presented Saturday August 29 and Sunday August 30, 2026 late-breaking prespecified subgroup analyses from the Phase 3 HELIOS-B trial of vutrisiran (AMVUTTRA, an RNAi therapeutic targeting transthyretin for transthyretin amyloidosis with cardiomyopathy, ATTR-CM) at ESC Congress 2026 Munich. Vutrisiran demonstrated consistent clinical benefit across all-cause mortality and recurrent cardiovascular events in patients with or without background tafamidis (the transthyretin tetramer stabilizer marketed as Vyndaqel/Vyndamax by Pfizer). The HELIOS-B trial had documented 28.2% reduction in all-cause mortality and 32.8% reduction in cardiovascular events with vutrisiran plus stabilizer. Additional analyses examined healthy aging, functional capacity, safety, and outcomes by sex. Alnylam also presented Amylo'ExTTRa, a large real-world analysis from the French National Health Data System characterizing the multisystem burden of ATTR-CM beyond cardiac manifestations. Vutrisiran anchors Alnylam's ATTR franchise alongside inclisiran (Leqvio, licensed to Novartis for hypercholesterolemia) and zilebesiran (Phase 3 ZENITH trial in hypertension).
Arrowhead Pharmaceuticals presented Phase 1/2a interim clinical data on ARO-INHBE at EASL 2026 today (Rinki Murphy, MBChB, PhD presenting). ARO-INHBE is an RNAi therapeutic targeting the Activin E/ALK7 pathway — a genetically validated regulator of adipose fat storage. The data: a single 400 mg dose produced 85.3% mean maximum Activin E reduction with persistent effect beyond 3 months; ≥200 mg doses reduced liver fat 44%. In combination with low-dose tirzepatide 5 mg in obese patients with type 2 diabetes, ARO-INHBE doubled weight loss and tripled reductions in visceral fat, total fat, and liver fat versus tirzepatide alone. Effect persists through Week 24 supporting potential twice-yearly dosing. Arrowhead is engaging with regulatory authorities on Phase 2 designs in MASH and obesity. The combination data is the strongest evidence to date that adding a non-GLP-1 mechanism to incretin therapy can meaningfully amplify body-composition outcomes — a contrast to the GLP-1-alone monotherapy story that has dominated obesity-pharmacology since 2021.