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Background: Enobosarm, a novel oral selective androgen receptor modulator, combined with a GLP-1 receptor agonist (RA) may prevent muscle loss, while preferentially reducing fat resulting in a higher quality weight loss. A meta-analysis was conducted of three randomized clinical studies of enobosarm involving older men, postmenopausal women, and older patients who have muscle loss due to advanced cancer. Loss of appetite occurs with advanced cancer inducing a starvation state similar to GLP-1 RA therapy. Methods: Meta-analysis was conducted of 3 randomized clinical trials evaluating enobosarm 3mg q day versus placebo and who had a Day 84 DXA scan to assess body composition: Phase 2 study in older males (60 yo) and postmenopausal women (n=48), Phase 2 study in patients with muscle wasting because of advanced cancer (n=61), and Phase 3 study in patients with advanced lung cancer (n=258). Results: At Day 84, DXA scan showed an absolute increase in lean mass of 1.5 kg in enobosarm treated vs placebo (p=0.00004) and % change in lean mass of a 4.04 % in enobosarm vs placebo (p=0.00007). Absolute decrease in fat mass was 0.758 kg in enobosarm treated vs placebo (p=0.015) and % change in fat mass was a loss -4.04 % in enobosarm vs placebo (p=0.006). Enobosarm was generally well tolerated with no increase in gastrointestinal side effects. Conclusion: In meta-analysis of 367 older men, postmenopausal women, and older patients with muscle loss from advanced cancer, enobosarm therapy resulted in reductions in fat mass while preserving lean mass. Meta-analysis supports the potential for enobosarm when combined with a GLP-1 RA may preserve muscle, while preferentially reducing fat resulting in a higher quality weight loss in overweight and obese patients. A Phase 2b randomized controlled trial is currently underway to evaluate enobosarm in older patients receiving a GLP-1 RA for weight loss. Disclosure J. Crawford: Advisory Panel; Pfizer Inc. Research Support; Pfizer Inc., AstraZeneca, helsinn. Advisory Panel; BioAtla. Consultant; Actimed. Advisory Panel; G1 Therapeutics, Enzychem. Consultant; Faraday. Advisory Panel; Jazz. A.S. Dobs: Speaker's Bureau; Halozyme. W.J. Evans: None. C. Prado: Speaker's Bureau; Abbott Nutrition, Nestlé Health Science, Nutricia, Amra medical. Advisory Panel; Pfizer Inc. D. Rodriguez: Employee; Veru. I. Shalev: Employee; Veru. K. Barnette: None. M. Steiner: Stock/Shareholder; Veru, Inc.
Crawford et al. (Fri,) studied this question.