Arrowhead Pharmaceuticals Begins Phase 1/2a Study of ARO-INHBE for Obesity Treatment

Arrowhead Pharmaceuticals, Inc., headquartered in Pasadena, California, has commenced dosing in a Phase 1/2a clinical trial for its experimental RNA interference (RNAi) treatment, ARO-INHBE. This therapeutic candidate is being explored as a potential solution for obesity. Concurrently, Arrowhead is seeking regulatory approval to begin trials for a second obesity-focused therapy, ARO-ALK7. Both ARO-INHBE and ARO-ALK7 aim to disrupt a pathway known for signaling the body to store fat in adipose tissue.

James Hamilton, M.D., Chief of Discovery and Translational Medicine at Arrowhead, emphasized the importance of the ARO-INHBE program to the company's strategic direction. He highlighted the promising preclinical outcomes that suggest this novel approach could reduce body weight while preserving lean muscle mass, contributing to better overall body composition. The ongoing Phase 1/2 trial will assess ARO-INHBE both as a standalone treatment and in combination with tirzepatide, with both segments targeting individuals with obesity.

ARO-INHBE works by diminishing the hepatic expression of the INHBE gene and its product, Activin E. The INHBE gene is a significant target due to its association with improved fat distribution and a reduced risk of metabolic conditions like type 2 diabetes when its function is impaired in humans. Activin E serves as a ligand in a metabolic pathway that controls energy balance in adipose tissues. By inhibiting this pathway, ARO-INHBE has the potential to enhance fat breakdown, reduce unhealthy fat accumulation and dysfunction, and improve insulin sensitivity.

The AROINHBE-1001 (NCT06700538) trial is a Phase 1/2a study designed to gradually increase dosages to evaluate the safety, tolerability, and pharmacological effects of ARO-INHBE in up to 78 obese adults. The first segment of the study focuses on single and multiple doses of ARO-INHBE alone, while the second segment examines its combined use with tirzepatide. Tirzepatide, a dual-action GLP-1/GIP receptor agonist, has been approved for managing type 2 diabetes in the U.S. and EU since 2022 and for weight management in recent years.

Arrowhead Pharmaceuticals specializes in developing therapies for difficult-to-treat diseases by targeting and silencing the genes responsible for them. The company utilizes a wide array of RNA chemistries and effective delivery systems to activate the RNA interference mechanism, leading to a swift and profound reduction in target gene expression. RNA interference is an intrinsic cellular mechanism that suppresses specific gene expressions, thereby influencing protein production. Arrowhead’s RNAi-based treatments capitalize on this natural gene-silencing process to achieve therapeutic effects.