Enobosarm Protects Lean Mass in Topline Phase 2b Trial Results

Topline data from the Phase 2b QUALITY trial showed enobosarm, a novel oral daily selective androgen receptor modulator (SARM), led to a statistically significant reduction in the loss of lean mass in patients receiving semaglutide (WEGOVY), a glucagon-like peptide-1 receptor agonist (GLP-1 RA), for weight reduction.1

Announced by Veru Pharmaceuticals, on January 27, 2025, the QUALITY trial, comparing enobosarm 3 mg and 6 mg to placebo in adults aged ≥60 years, met its primary endpoint, with additional positive effects on key secondary endpoints, including the change from baseline total fat mass, body composition, and physical function.

“This is the first clinical study to demonstrate prevention of both lean mass loss and decline in muscle function associated with weight loss in older individuals treated with a GLP-1 RA,” Louis Aronne, MD, past president of the Obesity Society, and a scientific advisor to Veru, said in a statement. “This combined treatment approach could benefit patients with obesity and low amounts of muscle due to age-related muscle loss.”

Estimates from the Centers for Disease Control and Prevention (CDC) have cited that nearly 42% of older adults with obesity could benefit from weight loss medications, with up to 34% of obese patients aged ≥60 having sarcopenic obesity.2 In the release, Veru indicated the potential risks of receiving GLP-1 medicines for weight loss, as their effect could accelerate muscle weakness in a subpopulation with critically low amounts of muscle due to aging.1

QUALITY evaluated the effects of enobosarm in 168 older patients aged ≥60 years with overweight or obesity who are receiving semaglutide for weight reduction. Topline efficacy analysis revealed a 71% reduction in the loss of lean mass, compared with placebo, for all patients receiving enobosarm and semaglutide at 16 weeks (P = .002).

Key secondary endpoints showed enobosarm led to 27% greater fat mass loss than placebo at 16 weeks (P = .096), with similar body weight changes (–4.7 vs. –4.4 kg). Further, compared with placebo, enobosarm also achieved a 70.5% reduction in weight loss due to lean mass, suggesting a more selective loss of fat mass.

Enobosarm also reduced the proportion of patients who lost clinically significant physical function versus patients receiving semaglutide alone. Approximately 54.5% fewer patients treated with enobosarm displayed a ≥10% decline in stair climb power, compared with the placebo group.

Safety data from QUALITY has remained blinded and will be available when the Phase 2b extension set is completed in April 2025. Aggregate blinded data did not reveal significant differences compared with the large safety database of 27 clinical trials investigating enobosarm in more than 1500 adults. Notably, enobosarm has not increased the rate of gastrointestinal adverse events, a key win as GLP-1 RA treatment is associated with significant and frequent gastrointestinal side effects.

The ongoing Phase 2b extension study will measure weight loss maintenance with enobosarm 3 mg or 6mg for an additional 12 weeks. Veru announced plans to present the full QUALITY efficacy and safety data set at future scientific conferences after unblinding the Phase 2b extension.

Veru also announced plans to seek an end-of-Phase 2 meeting with the FDA, citing the agency’s updated weight reduction guidance. Based on this guidance, enobosarm is being developed as a body composition drug to selectively preserve lean body mass, enhance physical function, and reduce fat in older overweight or obese patients on GLP-1 RA therapy for chronic weight management.

The FDA has already provided the company guidance on enobosarm’s regulatory path and Phase 3 trial design, with a proposed primary objective of the effect of enobosarm on stair climb power over 52 weeks.

“Older patients who have obesity or who are overweight and are receiving a GLP-1 RA are an ideal target population that have demonstrated in the Phase 2b QUALITY clinical study clinical benefit with enobosarm treatment to provide a greater quality weight loss as lean mass and physical function may be preserved with greater and selective loss of adiposity, that is, better body composition weight reduction may be possible,” Gary Barnette, PhD, chief scientific officer at Veru, said in a statement.

References

1. Veru announces positive topline data from Phase 2B Quality Clinical Study: ENOBOSARM preserved lean mass in patients receiving WEGOVY® (SEMAGLUTIDE) for weight reduction. Veru Inc. January 27, 2025. Accessed January 27, 2025. https://ir.verupharma.com/news-events/press-releases/detail/225/veru-announces-positive-topline-data-from-phase-2b-quality.
2. Batsis JA, Villareal DT. Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies. Nat Rev Endocrinol. 2018;14(9):513-537. doi:10.1038/s41574-018-0062-9