Arrowhead Pharmaceuticals Launches Phase 1/2a Trial of ARO-ALK7 for Obesity Treatment

PASADENA, CA, USA I June 02, 2025 I Arrowhead Pharmaceuticals, Inc. has announced the commencement of a Phase 1/2a clinical trial for ARO-ALK7, its experimental RNA interference (RNAi) therapeutic aimed at combating obesity. The trial marks the initial dosing of participants to evaluate the potential of ARO-ALK7, which targets a specific biological pathway involved in fat storage in the body. This investigational therapy will be tested in two stages: first, as a standalone treatment in healthy obese individuals, and subsequently in combination with the drug tirzepatide for patients with obesity, with or without type 2 diabetes.

ARO-ALK7 is designed to inhibit the expression of the ACVR1C gene in adipocytes, which are fat cells. This gene is crucial in the production of Activin receptor-like kinase 7 (ALK7), a receptor involved in maintaining energy balance within fat tissues. Genetic studies indicate that lower expression of ACVR1C correlates with healthier fat distribution and a reduced risk of complications associated with obesity. Preclinical animal research has demonstrated that silencing ALK7 in fat tissue results in decreased body weight and fat mass while preserving lean muscle mass. The potential of ARO-ALK7 is not only to decrease visceral fat but also to improve lipid profiles and glycemic control.

The clinical trial, known as AROALK7-1001 (NCT06937203), is a pioneering first-in-human dose-escalating study designed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of ARO-ALK7. This trial plans to enroll up to 90 obese adult volunteers. The study is divided into two parts: the first focuses on evaluating single and multiple doses of ARO-ALK7 alone, while the second part examines its effectiveness in combination with tirzepatide. Tirzepatide, a GLP-1/GIP receptor co-agonist delivered via subcutaneous injection, has been approved for type 2 diabetes management in both the United States and the European Union since 2022 and for weight management since 2023/2024.

Arrowhead Pharmaceuticals specializes in the development of therapeutics that address difficult-to-treat diseases by silencing the genes responsible for them. The company's methods employ a wide range of RNA chemistries and highly efficient delivery systems to activate the RNA interference mechanism. This approach leads to a rapid, profound, and lasting reduction in the expression of target genes. RNA interference (RNAi) is an inherent cellular process that inhibits gene expression, thereby affecting the production of specific proteins. Arrowhead's RNAi-based treatments utilize this natural gene-silencing pathway to develop innovative therapeutics.

Overall, the initiation of this clinical trial represents a significant step forward for Arrowhead Pharmaceuticals in its mission to provide effective treatments for obesity and related metabolic disorders. By targeting the underlying genetic drivers of these conditions, the company hopes to offer new therapeutic options that can lead to meaningful improvements in patient outcomes.