trevogrumab (REGN1033) / Regeneron, Sanofi - LARVOL DELTA

Lipid Effects of Trevogrumab and Garetosmab in Addition to Semaglutide Treatment in People Living with Obesity: Results from the COURAGE Study (AHA 2026) - "Abstract is embargoed at this time."

Genetic Disorders • Obesity

S46: Preserving muscle during GLP-1 RA treatment: insights from the trevogrumab COURAGE study (EASD 2026) - No abstract available

Metabolic Disorders

Cardiac safety of myostatin and activin A inhibition with trevogrumab and garetosmab in adults living with obesity: echocardiographic assessment from COURAGE phase 2 study (EASD 2026) - P2 | "Myostatin inhibition with TREVO ± activin A inhibition with GAR, on top of SEMA, revealed no adverse cardiac safety signals with respect to LVM or systolic function at 26 weeks, supporting the cardiac safety of these agents in adults living with obesity."

Clinical • P2 data • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Trevogrumab (an anti-myostatin) mitigates semaglutide‑associated lean body mass loss in adults with obesity and fully restores lean mass after semaglutide is discontinued (EASD 2026) - P2 | "Materials and People with obesity (BMI ≥30 kg/m 2 ), without type 2 diabetes (N = 599), were randomized 1:1:1:1 to receive semaglutide titrated up to 2.4 mg (SC QW) alone or in combination with trevogrumab 200 mg (SC QW), or trevogrumab 400 mg (SC QW) ± garetosmab (anti-activin A, 10 mg/kg IV Q4W), or placebos for 26 weeks (treatment period 1, TP1). Trevogrumab effectively minimized lean mass loss during GLP1-RA treatment and fully restored lean mass after GLP1-RA discontinuation."

Clinical • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Trevogrumab (anti-myostatin) preserves lean mass assessed by DXA during semaglutide-induced weight loss in adults living with obesity: 26-week dose-optimisation results from COURAGE Part C (EASD 2026) - P2 | "At 26 weeks, TREVO 75 mg mitigated approximately half of SEMA-associated reduction in LM without attenuating FM reduction. Notably, this effect was comparable to that observed with higher doses of TREVO (200 mg and 400 mg SC QW) in the previously presented COURAGE Part B study, suggesting that 75 mg may represent an optimal dose for muscle preservation during GLP-1 RA-induced weight loss, warranting further evaluation in future studies."

Clinical • Metabolic Disorders • Obesity

Trevogrumab, an anti-myostatin, attenuates lean mass loss during semaglutide treatment in people living with obesity with or without low lean mass at baseline (EASD 2026) - P2 | "TREVO at doses of 25 mg, 75 mg, 200 mg, and 400 mg attenuates LM loss during treatment with SEMA in people living with obesity, with or without OLLMM at baseline. Improvements appeared numerically greater in those with OLLMM at baseline. These findings support further investigation in individuals with pre-existing OLLMM, a population at elevated risk for functional impairment."

Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Effect of the anti-myostatin trevogrumab on semaglutide-associated thigh muscle volume loss in adults living with obesity: results from the COURAGE phase 2 MRI substudy (EASD 2026) - P2 | "At 26 weeks, TREVO 75 mg preserved 77% of SEMA-induced TMV loss, driven by preservation of FFMV. The greater reduction in MFI with TREVO also suggests a favorable effect on muscle composition. These results support the potential of TREVO, in combination with SEMA, to preserve skeletal muscle mass during GLP-1 RA-induced weight loss."

Clinical • P2 data • Metabolic Disorders • Obesity

Population-Normed Z-scores for Body Composition Enhance Sensitivity and Effect Size: Analysis of a Phase 2 RCT Testing Anti-GDF8 and Anti-Activin A on Top of Semaglutide (COURAGE) (ADA 2026) - P2 | "Z-scores were assessed in the COURAGE trial (NCT06299098), which tested the efficacy of semaglutide vs semaglutide with trevogrumab (anti-GDF8) with or without garetosmab (anti-activin A) for weight, TFM loss, and TLM preservation. The NHANES dataset (n = 26,125) was used to model the distributions of TLM and TFM as functions of covariates. Z-scores account for differences in weight loss across arms, yielding a larger effect size and greater sensitivity to group differences than percent CFB."

Clinical • P2 data • Metabolic Disorders

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 (ADA 2026) - "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."

Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

New Research on Muscle Biology and Body Composition in Metabolic Disease at ADA (The Manila Times) - "Four abstracts at ADA reflect Regeneron's investment in understanding and addressing muscle loss across metabolic disease. Three abstracts from the Phase 2 COURAGE trial examine the effects of trevogrumab (anti-GDF8) on lean mass in people with obesity treated with semaglutide, and an additional abstract will provide early preclinical research on muscle biology."

P2 data • Preclinical • Obesity

Opportunities to Reduce Patient Burden in Clinical Trials for People Living With Obesity in the US (OBESITY WEEK 2025) - "Therapies, including bimagrumab (anti-activin type II), trevogrumab (anti-myostatin) and garetosmab (anti-activin A), aim to improve the quality of weight loss by preserving lean mass and augmenting the amount of weight loss attributable to fat mass. Integrating the perspective of people living with obesity will ensure that clinical trials are reflective of real-world experiences, reducing patient burden, improving recruitment and retention and ultimately generating high quality data."

Clinical • Genetic Disorders • Obesity

Pharmacological intervention: Challenges and promising outcomes for fat loss and preservation of lean body mass in the treatment of overweight and type 2 diabetes. (PubMed, Diabetes Obes Metab) - "Activin II receptor inhibition with bimagrumab demonstrated significant preservation and increases in LBM, along with FM reduction, in both preclinical and phase 2 studies in individuals with overweight and T2D. Similar effects were observed for myostatin and activin A inhibitors (trevogrumab, garetosmab), latent myostatin inhibitors (apitegromab, SRK-439), and Selective Androgen Receptor Modulators (enobosarm)...Pharmacological adjunct therapies show potential for improving body composition and physical function during GLP-1 RA-induced weight loss. Preliminary findings are promising, but larger, controlled trials are necessary to confirm efficacy and safety before clinical implementation can be considered."

Journal • Review • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

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 (GlobeNewswire) - "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."

P2 data • Obesity

Anti-Myostatin (trevogrumab) with and without anti-Activin a (garetosmab) preserves lean mass and increases loss of fat mass in people with obesity treated with semaglutide (EASD 2025) - P2 | "A weight management strategy combining trevo with or without garet on top of sema is associated with LM preservation and greater FM loss. The full dataset of this study will be presented at EASD."

Late-breaking abstract • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

COURAGE: A Study to Test if Trevogrumab or Trevogrumab With Garetosmab When Taken With Semaglutide is Safe and How Well They Work in Adult Patients With Obesity for Weight Loss, Fat Loss, and Lean Mass Preservation (clinicaltrials.gov) - P2 | N=1005 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity • APOB

Interim Results from Ongoing Phase 2 COURAGE Trial Confirm Potential to Improve the Quality of Semaglutide (GLP-1 receptor agonist)-induced Weight Loss by Preserving Lean Mass (Regeneron Pharmaceuticals Press Release) - P2 | N=999 | COURAGE (NCT06299098) | Sponsor: Regeneron Pharmaceuticals | "Regeneron...announced interim results 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 trial demonstrated that approximately 35% of semaglutide-induced weight loss was due to loss of lean mass, and further demonstrated that combining semaglutide with trevogrumab with or without garetosmab helped preserve lean mass while increasing loss of fat mass. The interim analysis was conducted when 50% of patients reached week 26 in the trial. The combination of semaglutide with trevogrumab was generally well-tolerated; the triplet combination of semaglutide with both antibodies had a substantially higher rate of discontinuations due to tolerability issues and other adverse events..."

P2 data • Obesity

COURAGE: A Study to Test if Trevogrumab or Trevogrumab With Garetosmab When Taken With Semaglutide is Safe and How Well They Work in Adult Patients With Obesity for Weight Loss and Fat Loss (clinicaltrials.gov) - P2 | N=999 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Active, not recruiting ➔ Recruiting | Trial completion date: Aug 2026 ➔ Nov 2026 | Trial primary completion date: Feb 2026 ➔ May 2026

Enrollment open • Trial completion date • Trial primary completion date • Genetic Disorders • Obesity • APOB

Select Upcoming 2025 Milestones (GlobeNewswire) - "Report additional data from Phase 1/2 study for DB-OTO (AAV-based gene therapy) in patients with hearing deficit due to variants of the otoferlin gene (mid-2025); Report results from Phase 3 study for pozelimab (C5 antibody) in combination with cemdisiran in myasthenia gravis (second half 2025)....Report results from Phase 2 study for semaglutide in combination with trevogrumab (myostatin antibody) with and without garetosmab (Activin A antibody) in obesity (second half 2025); Report results from Phase 2 study for mibavademab (LEPR agonist antibody) in combination with tirzepatide in obesity (second half 2025); Report results from Phase 3 study for garetosmab (Activin A antibody) in fibrodysplasia ossificans progressiva (FOP) (second half 2025)."

Clinical data • Myasthenia Gravis • Obesity • Rare Diseases

The impact of weight loss on fat-free mass, muscle, bone and hematopoiesis health: Implications for emerging pharmacotherapies aiming at fat reduction and lean mass preservation. (PubMed, Metabolism) - "Novel compounds in the pipeline, such as Bimagrumab, Trevogrumab, and Garetosmab-which inhibit activins and myostatin signaling-have demonstrated promise in preventing muscle loss while promoting fat loss...Since this dual therapeutic approach could help address the challenges of muscle and bone loss during weight loss, well-designed studies are needed to optimize these strategies and assess long-term benefits. For the time being, considerations like advanced age and prefrailty may affect the choice of suitable candidates in clinical practice for current and emerging anti-obesity medications due to the associated risk of sarcopenia."

Journal • Review • Cardiovascular • Diabetes • Genetic Disorders • Hematological Disorders • Metabolic Disorders • Obesity • Osteoporosis • Sarcopenia

COURAGE: A Study to Test if Trevogrumab or Trevogrumab With Garetosmab When Taken With Semaglutide is Safe and How Well They Work in Adult Patients With Obesity for Weight Loss and Fat Loss (clinicaltrials.gov) - P2 | N=999 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

Combined GDF8 and Activin A Blockade in Healthy Volunteers: Safety, Efficacy, and Pharmacokinetics (OBESITY WEEK 2024) - "In healthy participants, trevogrumab and garetosmab were generally well tolerated. Combination tx led to greater-than-additive increases in muscle mass, with reductions in fat. Results suggest that GDF8 and activin A are key negative regulators of muscle mass in humans and that combination blockade may be a promising therapeutic approach in muscle atrophy and obesity settings."

Clinical • PK/PD data • Genetic Disorders • Muscular Atrophy • Obesity

COURAGE: A Study to Test if Trevogrumab or Trevogrumab With Garetosmab When Taken With Semaglutide is Safe and How Well They Work in Adult Patients With Obesity for Weight Loss and Fat Loss (clinicaltrials.gov) - P2 | N=999 | Recruiting | Sponsor: Regeneron Pharmaceuticals | N=624 ➔ 999 | Trial primary completion date: Jun 2026 ➔ Feb 2026

Enrollment change • Trial primary completion date • Genetic Disorders • Obesity

COURAGE: A Study to Test if Trevogrumab or Trevogrumab With Garetosmab When Taken With Semaglutide is Safe and How Well They Work in Adult Patients With Obesity for Weight Loss and Fat Loss (clinicaltrials.gov) - P2 | N=624 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Active, not recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

The Effect of Combined Activin A and Myostatin Blockade on Body Composition—A Phase 1 Trial (ADA 2024) - "Combined administration of trevogrumab and garetosmab led to dose-dependent, greater‑than‑additive increases in TMV and lean mass, while decreasing fat mass in healthy participants."

P1 data • Diabetes • Metabolic Disorders

COURAGE: A Study to Test if Trevogrumab or Trevogrumab With Garetosmab When Taken With Semaglutide is Safe and How Well They Work in Adult Patients With Obesity for Weight Loss and Fat Loss (clinicaltrials.gov) - P2 | N=624 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity