Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) has announced that it has filed for regulatory approval to launch a Phase 1/2a clinical trial for ARO-INHBE, its investigational RNA interference (RNAi) therapeutic aimed at treating obesity. The company also plans to seek regulatory clearance by the end of 2024 for its second obesity candidate, ARO-ALK7.
James Hamilton, M.D., Chief of Discovery and Translational Medicine at Arrowhead, stated, “Both ARO-INHBE and ARO-ALK7 are designed to target the same pathway responsible for fat storage in adipose tissue. Our preclinical data has shown promising results, indicating that targeting these pathways can reduce body mass and fat mass while preserving lean muscle mass, thereby improving body composition.” The initial Phase 1/2 study will consist of two parts: Part 1 will assess the safety and efficacy of single and multiple doses of ARO-INHBE in patients with obesity, while Part 2 will evaluate the effects of ARO-INHBE in combination with tirzepatide in both diabetic and non-diabetic patients with obesity. Hamilton emphasized the potential of these innovative therapeutic strategies to significantly influence obesity treatment.
ARO-INHBE targets the hepatic expression of the INHBE gene and its secreted product, Activin E. This gene is genetically validated; humans with loss-of-function variants in INHBE have a lower risk of obesity and metabolic diseases, including type 2 diabetes. Activin E plays a crucial role in regulating energy balance in adipose tissue. By intervening in this pathway, ARO-INHBE may enhance lipolysis and decrease adipose tissue hypertrophy, dysfunction, visceral fat, and insulin resistance.
The application to initiate the clinical trial has been submitted to the New Zealand Medicines and Medical Devices Safety Authority for review by the Standing Committee on Therapeutic Trials. If approved, Arrowhead will move forward with AROINHBE-1001, a Phase 1/2a dose-escalating study designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ARO-INHBE in up to 78 adult volunteers with obesity. Part 1 will focus on ARO-INHBE monotherapy, while Part 2 will investigate the combination with tirzepatide, a GLP-1/GIP receptor co-agonist that has been approved in the U.S. and EU for managing type 2 diabetes since 2022 and for weight management since 2023/2024.
