Veru Inc. presented a meta-analysis at ObesityWeek 2024, suggesting that enobosarm, a selective androgen receptor modulator (SARM), has the potential to optimize weight loss by preserving muscle mass. The presentation highlighted findings from four previous randomized clinical trials. The company is currently evaluating enobosarm in a Phase 2b clinical trial to further assess its efficacy in preserving muscle and augmenting fat loss in sarcopenic obese or overweight elderly patients receiving semaglutide (Wegovy®).
Enobosarm Phase 2b Clinical Trial Details
The ongoing Phase 2b trial is a multicenter, double-blind, placebo-controlled, randomized, dose-finding study. It aims to evaluate the safety and efficacy of enobosarm at 3mg and 6mg doses, compared to placebo, in 168 patients with sarcopenic obesity or who are overweight and over 60 years of age. All participants are also receiving semaglutide. The primary endpoint is total lean body mass, with key secondary endpoints including total body fat mass and physical function, measured by a stair climb test at 16 weeks. The trial is actively enrolling patients at up to 15 clinical sites in the United States, and topline results are expected in January 2025.
Following the initial 16-week efficacy assessment, participants will continue in a blinded Phase 2b extension trial. In this extension, all patients will discontinue their GLP-1 receptor agonist (RA) treatment but will continue receiving either placebo, enobosarm 3mg, or enobosarm 6mg for an additional 12 weeks. This extension study will evaluate whether enobosarm can maintain muscle mass and prevent fat and weight regain after discontinuing GLP-1 RA therapy. Topline results from the extension study are expected in Q2 2025.
Addressing Sarcopenic Obesity
According to the CDC, 41.5% of older adults in the United States are obese, and up to 34.4% of obese individuals over 60 have sarcopenic obesity. This condition is characterized by critically low muscle mass, making these patients particularly vulnerable to the adverse effects of GLP-1 RA drugs, which can further exacerbate muscle loss. The rapid muscle loss associated with GLP-1 RA therapy may accelerate frailty in older obese or overweight individuals, leading to poor balance, decreased gait speed, mobility issues, falls, fractures, and increased mortality.
Enobosarm's Mechanism and Safety Profile
Enobosarm is an oral, selective androgen receptor modulator (SARM) that has been studied in five previous clinical trials involving 968 older men and postmenopausal women, as well as older patients with muscle wasting due to advanced cancer. These trials suggest that enobosarm leads to dose-dependent increases in muscle mass, improvements in physical function, and reductions in fat mass. The data support the hypothesis that enobosarm, when combined with a GLP-1 RA, could augment fat reduction and total weight loss while preserving muscle mass.
Enobosarm has a large safety database, including 27 clinical trials involving 1581 men and women, with some patients dosed for up to 3 years. The data indicates that enobosarm is generally well-tolerated, with no increases in gastrointestinal side effects, which are commonly associated with GLP-1 RA treatment alone.
