Arrowhead Pharmaceuticals ARO-INHBE EASL 2026 (May 27): RNAi-Based Activin E/ALK7 Pathway Therapeutic Cuts Liver Fat 44% at ≥200 mg; Doubles Weight Loss + Triples Fat Reduction in Combination With Tirzepatide
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.