1230-OR: Lean Mass Effects of Anti-GDF8 (Trevogrumab) ± Anti-Activin A (Garetosmab) in People Living with Obesity Treated with Semaglutide with or without Low Lean Mass at Baseline

Introduction and Objective: Weight loss is associated with a significant reduction of lean mass (LM). The effects of GLP-1 therapy in patients with pre-existing low LM (LLM) are not well characterized. Here, we analyze the effects of trevogrumab (trevo) with and without garetosmab (garet) in people living with obesity with and without LLM at baseline and treated with semaglutide (sema). Methods: In a prespecified analysis of the phase 2 COURAGE trial by LLM status at baseline, participants with obesity without type 2 diabetes (N=599), were randomized 1:1:1:1 to receive sema titrated up to 2.4mg alone, in combination with trevo 200mg, 400mg, or 400mg + garet 10 mg/kg (triplet). Percent change in LM was measured by DXA from baseline to Week 26. Efficacy analyses were conducted using mixed models for repeated measures. Results: Overall, there was significantly less LM loss in the trevo 200mg, 400mg, and triplet groups vs sema alone, for participants with LLM (-2.8%, -3.4%, -2.5% vs -7.1%, respectively) and without LLM at baseline (-3.8%, -4.0%, -1.8% vs -5.9%, respectively) (Figure). Conclusion: Anti-GDF8 with or without anti-activin A on-top of sema preserved LM when compared to sema alone in individuals with obesity, regardless of pre-existing LLM at baseline. Additional research is needed to determine the potential benefit of reduced LM loss. Disclosure J. Chao: Employee; Current; Regeneron Pharmaceuticals Inc. A. Templeton: Employee; Current; Regeneron Pharmaceuticals Inc. Y. Yao: None. J.G. Raya: Employee; Current; Regeneron Pharmaceuticals Inc. Stock/Shareholder; Current; Regeneron Pharmaceuticals Inc. A. Vavere: Employee; Current; Regeneron Pharmaceuticals Inc. Employee; Ended; AstraZeneca. Stock/Shareholder; Current; AstraZeneca, Regeneron Pharmaceuticals Inc. A.V. Sorokin: None. J. Lighter: None. O. Mosenzon: Employee; Current; Regeneron Pharmaceuticals Inc. Stock/Shareholder; Current; Regeneron Pharmaceuticals Inc. R.A. Calle: Employee; Current; Regeneron Pharmaceuticals Inc. Stock/Shareholder; Current; Regeneron Pharmaceuticals Inc. Stock/Shareholder; Ended; Pfizer Inc.