Arrowhead Pharmaceuticals has dosed the first subjects in a Phase 1/2a clinical trial of ARO-INHBE, the company’s investigational RNA interference (RNAi) therapeutic being developed as a potential treatment for obesity. Arrowhead also filed recently a request for regulatory clearance to initiate a clinical trial for its second obesity candidate, ARO-ALK7. Both ARO-INHBE and ARO-ALK7 are designed to intervene in a known pathway that signals the body to store fat in adipose tissue.
ARO-INHBE is designed to reduce the hepatic expression of the INHBE gene and its secreted gene product, Activin E. INHBE is a promising genetically validated target in which loss-of-function INHBE variants in humans are associated with improved fat distribution and lower risk of metabolic diseases, such as type 2 diabetes. Activin E acts as a ligand in a pathway that regulates energy homeostasis in adipose tissue. Inhibiting this pathway with investigational ARO-INHBE treatment has the potential to increase lipolysis, and reduce adipose hypertrophy and dysfunction, visceral adiposity, and insulin resistance.
“ARO-INHBE is an important programme for Arrowhead that complements our strategic focus on developing and commercializing important RNAi-based therapies for cardiometabolic diseases. Further, our preclinical studies have yielded promising results for this novel mechanism to reduce body weight and potentially preserve lean muscle mass resulting in improved body composition,” said Dr James Hamilton, Chief of Discovery and Translational Medicine at Arrowhead. “The Phase 1/2 study will evaluate ARO-INHBE as a monotherapy in part 1 and as a combination therapy with tirzepatide in part 2, with both parts enrolling patients with obesity.”
AROINHBE-1001 is a Phase 1/2a dose-escalating study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ARO-INHBE in up to 78 adult volunteers with obesity. Part 1 of the study is designed to assess single and multiple doses of ARO-INHBE monotherapy, and Part 2 of the study is designed to assess ARO-INHBE in combination with tirzepatide, a subcutaneously administered GLP-1/GIP receptor co-agonist that has been approved in the US and the European Union for management of type 2 diabetes mellitus since 2022 and weight management since 2023/2024 respectively.
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