Regeneron announces updated analyses from Phase 2 COURAGE trial

Regeneron (REGN) Pharmaceuticals announced updated analyses from the ongoing Phase 2 COURAGE trial investigating novel combinations of semaglutide and trevogrumab with or without garetosmab for the treatment of obesity. The complete 26-week results were consistent with interim data previously reported, demonstrating that the addition of trevogrumab with or without garetosmab could significantly reduce the loss of lean mass associated with semaglutide-induced weight loss; the results confirmed that 33% of weight loss induced by semaglutide was due to loss of lean mass, and that adding trevogrumab could prevent about half of this lean mass loss. The results were presented as a late-breaking oral session at the 61st Annual Meeting of the European Association for the Study of Diabetes in September 2025. COURAGE was designed to investigate the quality of weight loss in patients with obesity. Treatment is divided into two 26-week periods comprised of a weight-loss phase and a weight-maintenance phase. The three primary efficacy endpoints were assessed in this analysis at week 26, and included percent change from baseline at week 26 in lean mass, fat mass and body weight. During the weight-loss phase, patients were randomized to receive semaglutide 2.4 mg alone or in combination with trevogrumab 200 mg, trevogrumab 400 mg or higher-dose trevogrumab plus garetosmab 10 mg/kg. At this analysis, 33% of semaglutide-induced weight loss was due to lean mass loss, while patients in all combination groups had improvement in body composition including lean mass preservation and greater fat loss compared to semaglutide alone. Numerical improvements in metabolic and lipid parameters, secondary and exploratory endpoints, were seen across all treatment groups, including improvements in waist circumference, blood pressure, cholesterol, triglycerides and A1C. The combination of semaglutide with trevogrumab was generally well-tolerated; Adverse events that occurred in greater than or equal to5% of participants in any treatment group included muscle spasms, nausea, constipation, fatigue, diarrhea, headache, vomiting, gastroesophageal reflux disease, upper respiratory tract infection, nasopharyngitis, UTI, influenza and COVID-19. Most of these events were mild to moderate in severity. As previously reported, the triplet combination of semaglutide with both antibodies had a substantially higher rate of discontinuations due to tolerability issues and other adverse events. Two deaths occurred in the triplet group, one due to an undetermined cause in a patient with multiple cardiovascular risk factors and the second due to a cardiac arrest in a person with a history of cardiovascular disease. Regeneron has not identified a causal association between treatment and these events. After 26 weeks, patients enter into the weight-maintenance phase in which they receive either higher-dose trevogrumab monotherapy or placebo through the end of the trial. The safety and efficacy of trevogrumab and garetosmab have not been evaluated by any regulatory authority.