#1782591 Potential to Optimize Weight Loss with Enobosarm: Augment Reduction of Fat Mass while Preserving Muscle in Older Patients with Obesity

There is a need for a drug when combined with a GLP-1 receptor agonist (RA) can prevent muscle loss, while preferentially reducing fat resulting in high quality weight loss. Older sarcopenic obese patients receiving a GLP-1 RA are at the highest risk for muscle atrophy and muscle weakness leading to frailty. Enobosarm, a novel oral selective androgen receptor modulator, has been studied in 5 clinical muscle studies involving 968 older men, postmenopausal women, and older patients who have muscle loss due to advanced cancer. The totality of the clinical data demonstrates that enobosarm therapy results in dose-dependent reductions in fat mass and increases in muscle mass with improvement in physical function. A placebo controlled Phase 3 clinical trial was conducted evaluating 3mg enobosarm for the treatment of muscle wasting in advanced lung cancer patients undergoing chemotherapy. A post-hoc analysis was performed to assess body composition by DXA scan in a subset of older (≥60 years) patients with obesity (BMI ≥ 30kg/m2) at 12 and 21 weeks. Loss of appetite occurs with advanced cancer inducing a starvation state similar to GLP-1 RA therapy. At 12 weeks, enobosarm 3mg treated subjects had 4.96% increase in total lean mass compared to placebo and a 5.77% reduction in fat mass compared to placebo (n=29). By 21 weeks, enobosarm 3mg treatment resulted in a 14.4% total fat mass loss, and a 4.5% loss of DXA body weight compared to placebo while maintaining lean mass (Figure 1). Enobosarm was generally well tolerated with no increase in gastrointestinal side effects. In a subset analysis of older obese patients, enobosarm therapy resulted in reductions in fat mass while preserving lean body mass (muscle) leading to greater high quality weight loss. A Phase 2b randomized controlled trial is currently underway to evaluate the safety and efficacy of enobosarm in preserving muscle mass and augmenting fat loss in at risk sarcopenic obese or overweight older patients receiving a GLP-1 RA for weight loss.