Enobosarm Significantly Preserves Muscle Mass When Added to Semaglutide, Advances to Phase 3 Development Program
Enobosarm added to semaglutide shows promising results in preserving muscle mass while promoting fat loss in older adults, according to developer Veru, Inc.
The investigational selective androgen receptor modulator enobosarm, when added to treatment with semaglutide (enobosarm/semaglutide), was associated with highly selective loss of fat mass while preserving lean mass in adults aged 60 years and older treated for overweight or obesity, according to drug developer Veru.1
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In the phase 2b QUALITY clinical trial, 99% of total weight loss was attributable to fat among participants receiving semaglutide/enobosarm, translating to 1.2% loss of lean body mass compared with the 4.1% loss seen with semaglutide plus placebo (semaglutide/placebo).1
Adding to these findings, reported in January 2025, Veru announced on Wednesday2 the topline efficacy and safety data from the QUALITY study demonstrating that the combination of enobosarm/semaglutide as compared to enobosarm/placebo provoked no increase in adverse events (AEs), including gastrointestinal (GI) adverse events, drug-induced liver injury, or obstructive sleep apnea. There were no reports of suicidal ideation or of serious AEs, according to Veru. Four nontreatment-related SAEs were reported across the 2 groups.2
Based on the new safety findings, Veru has requested an End of phase 2 meeting with the FDA to provide regulatory clarity on the company’s phase 3 clinical program. Veru will advance enobosarm 3 mg as the proposed oral dose to be evaluated in the late-stage trials, according to a company statement.2
“The safety results from the Phase 2b study are positive and suggest that the addition of enobosarm to semaglutide treatment doesn’t worsen, and in some cases appears to improve gastrointestinal side effects,” Louis J. Aronne, MD, an obesity expert, past president of the Obesity Society and a scientific advisor and consultant to Veru, said in the statement.2
Veru anticipates the End of Phase 2 meeting will be scheduled for the third quarter this year. Further, the company expects to report topline efficacy and safety findings for the phase 2b maintenance study this quarter, "which will show us whether enobosarm monotherapy can stop the fat and weight regain that generally happens when patients discontinue GLP-1 receptor agonist treatment," Mitchell Steiner, MD, Veru chairmen, president, and CEO, said in the statement. The company said it plans to report the full phase 2b QUALITY and extension clinical trial data at future scientific meetings and to publish findings in clinical journals.2
The Phase 2b Quality Clinical Trial
The multicenter, double-blind, placebo-controlled, randomized, dose-finding trial evaluated enobosarm 3 mg and 6 mg vs placebo in adults aged 60 years and older receiving semaglutide for chronic weight management.
In the topline analysis of efficacy, the trial met the prespecified primary endpoint with a statistically significant and clinically meaningful benefit among participants receiving enobosarm/semaglutide—a 71% relative reduction in lean mass loss compared to semaglutide/placebo at 16 weeks (P =.002). The 3-mg dose proved most effective, showing a 99.1% mean relative reduction in loss of lean mass (P <.001), while the 6-mg dose provided no additional benefit.1
Secondary endpoints revealed dose-dependent fat mass reduction, with the 6-mg dose achieving 46% greater relative loss of fat mass compared to placebo plus semaglutide at 16 weeks (P =.014). Despite similar overall weight loss between groups as measured by DEXA, the composition of weight loss differed substantially. In the semaglutide/placebo group, lean mass accounted for 32% of total body weight loss with fat loss comprising 68%. Conversely, in the enobosarm 3-mg/semaglutide group, lean mass loss represented only 0.9% of total weight loss, with fat loss accounting for 99.1%.1
Physical function assessment using the Stair Climb Test demonstrated clinically relevant improvements. Using a greater than 10% decline in stair climb power at 16 weeks as the threshold—corresponding to approximately 7.5 years of age-related decline—42.6% of semaglutide/placebo participants experienced this decline compared to 16% in the enobosarm 3-mg group, for a 62.4% relative reduction (P =.006). In the 6-mg group 22.5% of participants experienced the decline, a 46.2% relative reduction compared to placebo (P= .05).1
The proposed Phase 3 trial will be a double-blind, placebo-controlled study in patients aged 60 years and older with obesity or overweight status eligible for GLP-1 receptor agonist treatment, potentially including both semaglutide and tirzepatide. The primary and secondary outcomes will be similar to those for the QUALITY trial.
The QUALITY study represents the first controlled trial demonstrating that older patients receiving GLP-1 receptor agonists face increased risk for accelerated lean mass loss and associated functional decline, while establishing enobosarm's potential to address this clinical challenge through selective fat loss and muscle preservation.1
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. News release. Veru Inc. January 27, 2025. Accessed May 29, 2025. https://ir.verupharma.com/news-events/press-releases/detail/225/veru-announces-positive-topline-data-from-phase-2b-quality
2. Veru reports positive safety results form phase 2b QUALITY study: enobosarm added to semaglutide led to greater fat loss, preservation of muscle, and fewer gastrointestinal side effects compared to semaglutide alone. News release. Veru, Inc. May 28, 2025. Accessed May 29, 2025. https://ir.verupharma.com/news-events/press-releases/detail/234/veru-reports-positive-safety-results-from-phase-2b-quality
