Arrowhead Pharmaceuticals has reported promising early-stage trial results showing that its RNA interference (RNAi) therapies can significantly enhance weight loss and improve body composition in patients with type 2 diabetes—potentially outperforming Eli Lilly’s tirzepatide when used in combination. The news sent Arrowhead shares up 17% to $75.20 in early trading Tuesday.
The interim findings come from two Phase I/IIa trials evaluating Arrowhead’s ARO-INHBE and ARO-ALK7. In a small cohort of four patients with type 2 diabetes, ARO-INHBE combined with tirzepatide led to an average weight reduction of 9.4% at week 16. In comparison, five patients treated with tirzepatide alone lost 4.8% of their body weight over the same period—roughly half the reduction achieved with the combination.
Beyond overall weight loss, ARO-INHBE also demonstrated a substantial impact on fat composition. In the tirzepatide combination group, reductions in visceral fat, total fat, and liver fat were approximately three times greater than those seen with tirzepatide alone, although this analysis was limited to three patients. When administered without tirzepatide, ARO-INHBE reduced visceral fat by 9.9%, liver fat by 38%, and increased lean tissue by 3.6%, achieving a placebo-adjusted visceral fat reduction of 15.6% at week 24.
Arrowhead framed these results as a proof of concept that targeting the Activin E pathway can improve body composition and enhance weight loss beyond current therapies, particularly for individuals with type 2 diabetes.
Safety data were encouraging. Treatment-emergent adverse events were mostly mild, with no discontinuations related to the therapy. One patient experienced a limb abscess, which was treated successfully and deemed unrelated to the study drugs. Gastrointestinal side effects were comparable between the combination therapy and tirzepatide-alone groups, and no clinically significant changes in liver enzymes, blood sugar levels, or lipid profiles were observed.
Arrowhead also shared initial results for ARO-ALK7, which targets the ACVR1C gene. The therapy achieved 88% silencing of adipose ALK7 mRNA by week eight and produced a placebo-adjusted 14.1% reduction in visceral fat. The treatment was well tolerated, the company said.
Analysts at Truist Securities described the weight loss observed with Arrowhead’s therapy as “substantial” and “meaningful.” While interest in weight loss composition has slowed amid the anticipated rollout of oral options from Eli Lilly and Novo Nordisk, Truist noted that Arrowhead’s findings could renew attention on combination and targeted therapies. Competing programs in this space include Scholar Rock’s apitegromab, Lilly’s bimagrumab, and Wave Life Sciences’ WVE-007.
Arrowhead expects additional data from both trials later this year and will host a conference call at 11:30 a.m. ET Tuesday to discuss results. The company, which secured its first FDA approval in November 2025 for plozasiran (Redemplo) to treat familial chylomicronemia syndrome, plans to continue developing both ARO-INHBE and ARO-ALK7 in-house.
The results could also benefit Eli Lilly. The combination approach may enhance tirzepatide’s performance without directly competing with Lilly’s upcoming oral weight loss drug, orforglipron, which could launch as early as March pending FDA approval.
