Arrowhead Pharmaceuticals announced interim Phase 1/2a clinical results from its RNA interference (RNAi)-based obesity programmes, reporting encouraging weight loss and body-composition improvements in obese adults, including patients with type 2 diabetes.
Preliminary findings show that ARO-INHBE, when combined with GLP-1/GIP receptor agonist tirzepatide, produced a -9.4% mean body-weight reduction at Week 16 in obese patients with type 2 diabetes, nearly double the weight loss seen with tirzepatide alone (-4.8%). The combination also delivered greater reductions in visceral fat (-23.2% vs -7.4%), total fat (-15.4% vs -5.3%) and liver fat (-76.7% vs -20%), based on MRI measures.
Arrowhead’s early human data also indicate potential benefits in body composition beyond weight loss. As monotherapy:
- ARO-INHBE reduced visceral fat by 9.9% and liver fat by 38% at Week 16, with a demonstrated increase in lean tissue.
- ARO-ALK7, the first RNAi therapeutic to silence an adipocyte-expressed target in humans, achieved up to 88% reduction in ALK7 mRNA and early mean visceral fat loss of 14% (placebo-adjusted) by Week 8. Both investigational agents were generally well tolerated in the interim dataset. Most reported adverse events were mild, with no discontinuations due to treatment-emergent events and no clinically significant laboratory trends observed.
The data are not only notable for enhanced weight loss compared with incretin therapy alone, but also for deep improvements in metabolic fat compartments, factors closely linked to cardiometabolic risk. Carel le Roux, M.D., Ph.D., Chair in Metabolic Medicine at University College Dublin, described the results as demonstrating that targeting the Activin E/ALK7 pathway may offer therapeutic leverage on disease drivers beyond mere calorie reduction.