Results from Phase 2 COURAGE Trial Demonstrating Potential to Improve Quality of GLP-1 receptor agonist-induced Weight Loss by Preserving Lean Mass, Presented at EASD

Complete 26-week results further demonstrate that combining semaglutide with trevogrumab (anti-GDF8/anti-myostatin) helped prevent about half of semaglutide-induced loss of lean mass, while increasing fat mass loss

Numeric improvements in metabolic and lipid parameters including waist circumference, blood pressure, cholesterol, triglycerides and A1C, were observed across all treatment groups

TARRYTOWN, N.Y., Sept. 17, 2025 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced updated analyses from the ongoing Phase 2 COURAGE trial investigating novel combinations of semaglutide (GLP-1 receptor agonist) and trevogrumab (anti-GDF8/anti-myostatin) with or without garetosmab (anti-activin A) 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 (EASD) in September 2025.

"These complete 26-week COURAGE results demonstrate a meaningful opportunity to preserve muscle mass while enhancing fat loss," said Julio Rosenstock, M.D., Lead PI and Senior Scientific Advisor Velocity Clinical Research at Medical City and Clinical Professor of Medicine, University of Texas Southwestern Medical Center, Dallas. “These encouraging early data, with positive trends in lipid parameters, warrant further studies to confirm the potential of trevogrumab’s role in preserving lean muscle mass during weight loss, especially in combination with incretin-related therapies.”

COURAGE was designed to investigate the quality of weight loss in patients with obesity (BMI ³30 kg/m²). 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 (end of weight-loss phase), 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 (lower dose), trevogrumab 400 mg (higher dose) or higher-dose trevogrumab plus garetosmab 10 mg/kg (triplet).

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. Detailed results of this analysis from baseline to week 26 include:

SE= Standard Error
NOTE: Lean mass and fat mass was calculated using dual-energy X-ray absorptiometry (DXA) scan, while body weight was measured using a scale; as a result, the lean and fat mass numbers may not exactly sum to body weight. Total weight loss is defined as the sum of lean mass loss and fat mass loss. Results are based on least-squares means derived from MMRM analysis using efficacy estimand that excludes data after the treatment discontinuation.
***p<0.001; *p<0.05; p-values are for the primary endpoints of % change from baseline at week 26 in each category, and were not corrected for multiplicity.

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 ≥5% 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 (week 52).

The safety and efficacy of trevogrumab and garetosmab have not been evaluated by any regulatory authority.

About Regeneron in Obesity
Obesity is a complex, multifaceted disease and a growing public health concern that affects more than a billion people worldwide. Despite the revolutionary impact of GLP-1 receptor agonists (GLP-1RAs) on weight loss, the quality of this weight loss can be negatively impacted because these agents can cause profound muscle loss. Moreover, a high percentage of patients cycle on and off treatment – while off treatment they can regain almost all of the weight lost, but mostly in the form of fat, leaving them with negatively altered body composition.

At Regeneron, we are developing a pipeline focused on the quality of weight reduction. We have several independent approaches focused on promoting and preserving muscle during weight loss, so as to increase the amount of fat loss since adiposity is the principal driver of comorbidities and metabolic diseases associated with obesity. In addition, Regeneron has an extensive pipeline of agents to address some of these co-morbidities and metabolic diseases, which have the potential to be combined with GLP-1RAs. The combination of our science, pipeline, research and clinical innovation uniquely positions us to make a meaningful difference in obesity and obesity-related diseases.  

About Regeneron's VelocImmune^® Technology
Regeneron's VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron's co-Founder, President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite^® technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create a substantial proportion of all original, FDA-approved fully human monoclonal antibodies. This includes Dupixent^® (dupilumab), Libtayo^® (cemiplimab-rwlc), Praluent^® (alirocumab), Kevzara^® (sarilumab), Evkeeza^® (evinacumab-dgnb), Inmazeb^® (atoltivimab, maftivimab and odesivimab-ebgn) and Veopoz^® (pozelimab-bbfg). In addition, REGEN-COV^® (casirivimab and imdevimab) had been authorized by the FDA during the COVID-19 pandemic until 2024.

About Regeneron
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous approved treatments and product candidates in development, most of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, neurological diseases, hematologic conditions, infectious diseases, and rare diseases.

Regeneron pushes the boundaries of scientific discovery and accelerates drug development using our proprietary technologies, such as VelociSuite^®, which produces optimized fully human antibodies and new classes of bispecific antibodies. We are shaping the next frontier of medicine with data-powered insights from the Regeneron Genetics Center^® and pioneering genetic medicine platforms, enabling us to identify innovative targets and complementary approaches to potentially treat or cure diseases.

For more information, please visit www.Regeneron.com or follow Regeneron on LinkedIn, Instagram, Facebook or X.

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A more complete description of these and other material risks can be found in Regeneron’s filings with the U.S. Securities and Exchange Commission, including its Form 10-K for the year ended December 31, 2024 and its Form 10-Q for the quarterly period ended June 30, 2025. Any forward-looking statements are made based on management’s current beliefs and judgment, and the reader is cautioned not to rely on any forward-looking statements made by Regeneron. Regeneron does not undertake any obligation to update (publicly or otherwise) any forward-looking statement, including without limitation any financial projection or guidance, whether as a result of new information, future events, or otherwise.

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