Arrowhead Pharmaceuticals is set to initiate clinical trials for two novel RNA interference (RNAi) therapies, ARO-INHBE and ARO-ALK7, targeting obesity and related metabolic conditions. The company has filed for regulatory clearance to begin a Phase 1/2a clinical trial of ARO-INHBE in New Zealand, with plans to submit for ARO-ALK7 before the end of the year. These therapies represent a new approach to obesity treatment by intervening in the pathway that signals the body to store fat in adipose tissue.
ARO-INHBE: Targeting INHBE Gene for Obesity Treatment
ARO-INHBE is designed to reduce the expression of the INHBE gene in the liver, which in turn reduces the secretion of Activin E. Loss-of-function variants in the INHBE gene are associated with a lower risk of obesity and metabolic diseases like type 2 diabetes. Preclinical studies have demonstrated that ARO-INHBE can reduce body weight and fat mass while potentially preserving lean muscle mass, a significant advantage over some existing obesity therapies.
James Hamilton, Chief of Discovery and Translational Medicine at Arrowhead, noted, "We have generated very promising preclinical data that suggests inhibition of these targets reduces body mass and fat mass but spares lean muscle mass resulting in improved body composition."
The planned Phase 1/2a study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ARO-INHBE in up to 78 adult volunteers with obesity. The study will consist of two parts: Part 1 will assess single and multiple doses of ARO-INHBE monotherapy, while Part 2 will evaluate ARO-INHBE in combination with tirzepatide, a GLP-1/GIP receptor co-agonist already approved for type 2 diabetes and weight management.
ARO-ALK7: Expanding the Obesity Pipeline
Arrowhead is also advancing ARO-ALK7, another RNAi therapy designed to intervene in the same pathway that signals the body to store fat. The company plans to file for regulatory clearance to initiate a clinical trial for ARO-ALK7 before the end of 2024.
Christopher Anzalone, CEO of Arrowhead Pharmaceuticals, stated that both drugs have "good genetic validation," and that the pathway used to signal the body to store fat is well understood.
RNAi-based Approach
Arrowhead's approach leverages RNA interference (RNAi), a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics trigger this natural pathway of gene silencing.
With these two drug candidates, Arrowhead Pharmaceuticals aims to address the growing need for effective and well-tolerated obesity treatments, potentially offering a novel approach that preserves lean muscle mass while reducing body weight and fat mass.
