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:

	Semaglutide monotherapy (n=151)	Lower-dose combo (n=149)	Higher-dose combo (n=152)	Triplet (n=147)
Lean mass
Percent change from baseline (SE)	-6.5 (0.5)	-3.3 (0.5)	-3.8 (0.5)	-2.0 (0.6)
Change in kg from baseline (% of total weight loss)	-3.3 kg (33.0%)	-1.5 kg*** (16.8%)	-1.9 kg*** (18.1%)	-0.9 kg*** (7.4%)
Fat mass
Percent change from baseline (SE)	-15.7 (0.9)	-17.3 (0.9)	-19.1 (0.9)	-27.1 (1.1)
Change in kg from baseline (% of total weight loss)	-6.7 kg (67.0%)	-7.6 kg (83.2%)	-8.5 kg* (81.9%)	-11.8 kg*** (92.6%)
Body weight
Percent change from baseline (SE)	-10.6 (0.5)	-9.9 (0.5)	-11.1 (0.5)	-13.4*** (0.6)

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.

Forward-Looking Statements and Use of Digital Media

This press release includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc. ("Regeneron" or the "Company"), and actual events or results may differ materially from these forward-looking statements. Words such as "anticipate," "expect," "intend," "plan," "believe," "seek," "estimate," variations of such words, and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. These statements concern, and these risks and uncertainties include, among others, the nature, timing, and possible success and therapeutic applications of products marketed or otherwise commercialized by Regeneron and/or its collaborators or licensees (collectively, "Regeneron's Products") and product candidates being developed by Regeneron and/or its collaborators or licensees (collectively, "Regeneron's Product Candidates") and research and clinical programs now underway or planned, including without limitation Regeneron's clinical program investigating novel combinations of semaglutide (GLP-1 receptor agonist) and high- or low-dose trevogrumab (anti-GDF8 /anti-myostatin) with or without garetosmab (anti-activin A) for the treatment of obesity as discussed in this press release; uncertainty of the utilization, market acceptance, and commercial success of Regeneron's Products and Regeneron's Product Candidates and the impact of studies (whether conducted by Regeneron or others and whether mandated or voluntary), including the studies discussed or referenced in this press release, on any of the foregoing or any potential regulatory approval of Regeneron's Products and Regeneron's Product Candidates (such as those referenced above); the likelihood, timing, and scope of possible regulatory approval and commercial launch of Regeneron's Product Candidates and new indications for Regeneron's Products, such as those referenced above for the treatment of obesity; the ability of Regeneron's collaborators, licensees, suppliers, or other third parties (as applicable) to perform manufacturing, filling, finishing, packaging, labeling, distribution, and other steps related to Regeneron's Products and Regeneron's Product Candidates; the ability of Regeneron to manage supply chains for multiple products and product candidates and risks associated with tariffs and other trade restrictions; safety issues resulting from the administration of Regeneron's Products and Regeneron's Product Candidates (such as those referenced above) in patients, including serious complications or side effects in connection with the use of Regeneron's Products and Regeneron's Product Candidates in clinical trials; determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron's ability to continue to develop or commercialize Regeneron's Products and Regeneron's Product Candidates; ongoing regulatory obligations and oversight impacting Regeneron's Products, research and clinical programs, and business, including those relating to patient privacy; the availability and extent of reimbursement or copay assistance for Regeneron's Products from third-party payors and other third parties, including private payor healthcare and insurance programs, health maintenance organizations, pharmacy benefit management companies, and government programs such as Medicare and Medicaid; coverage and reimbursement determinations by such payors and other third parties and new policies and procedures adopted by such payors and other third parties; changes in laws, regulations, and policies affecting the healthcare industry; competing drugs and product candidates that may be superior to, or more cost effective than, Regeneron's Products and Regeneron's Product Candidates (including biosimilar versions of Regeneron's Products); the extent to which the results from the research and development programs conducted by Regeneron and/or its collaborators or licensees may be replicated in other studies and/or lead to advancement of product candidates to clinical trials, therapeutic applications, or regulatory approval; unanticipated expenses; the costs of developing, producing, and selling products; the ability of Regeneron to meet any of its financial projections or guidance and changes to the assumptions underlying those projections or guidance; the potential for any license, collaboration, or supply agreement, including Regeneron's agreements with Sanofi and Bayer (or their respective affiliated companies, as applicable), to be cancelled or terminated; the impact of public health outbreaks, epidemics, or pandemics on Regeneron's business; and risks associated with litigation and other proceedings and government investigations relating to the Company and/or its operations (including the pending civil proceedings initiated or joined by the U.S. Department of Justice and the U.S. Attorney's Office for the District of Massachusetts), risks associated with intellectual property of other parties and pending or future litigation relating thereto (including without limitation the patent litigation and other related proceedings relating to EYLEA^® (aflibercept) Injection), the ultimate outcome of any such proceedings and investigations, and the impact any of the foregoing may have on Regeneron's business, prospects, operating results, and financial condition. 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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Contacts:
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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