bimagrumab (BYM338) / Novartis, Eli Lilly - LARVOL DELTA

Therapeutic advances in sarcopenia management: From traditional interventions to personalized medicine. (PubMed, Clin Nutr) - "Pharmacological trials highlight selective androgen receptor modulators (SARMs) and myostatin inhibitors (e.g., bimagrumab) increasing lean mass by 3-5% in phase II studies, with GDF-15-neutralizing antibodies emerging as promising anti-catabolic agents...This synthesis underscores the paradigm shift toward precision medicine but identifies critical knowledge gaps, including long-term safety of biologics and cost-effectiveness of regenerative approaches. Future research should prioritize multimodal therapies, validated biomarkers, and AI-driven algorithms to individualize sarcopenia management in aging populations."

Journal • Review • Geriatric Disorders • Inflammation • Sarcopenia • Targeted Protein Degradation • Transplantation • GDF15 • IGF1 • IL6 • TNFA

Safety and Efficacy of Bimagrumab and Semaglutide in Adults Who Are Overweight or Obese (clinicaltrials.gov) - P2 | N=507 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Obesity

Effect Of CDD866, An Anti-activin Type II Receptor Antibody, On The Melanocortin 3 Receptor (MC3R) Deficiency Obesity Phenotype (ENDO 2025) - "Bimagrumab (BYM338) is a humanized monoclonal antibody that binds to the activin type II receptor (ActRII) and inhibits its signal transduction, thus reducing negative regulation of skeletal muscle growth due to activin and/or myostatin...There were no significant group differences in percent fat mass or glucose and insulin tolerance, with trends toward increased fat mass and worsening glucose and insulin tolerance, following CDD866 administration. We conclude that the murine ActRII blocking antibody CDD866 increases lean mass in mice with MC3R deficiency but does not improve overall body composition or glucose homeostasis, suggesting that MC3R deficiency, and the associated dysregulation of fat and lean mass, is unlikely to be related to unduly increased ActRII activation."

Late-breaking abstract • Genetic Disorders • Obesity • ACVR2A

A Study of Bimagrumab Alone (LY3985863) and Bimagrumab With Tirzepatide (LY900042) in Healthy Participants (clinicaltrials.gov) - P1 | N=100 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

Enrollment closed

Bimagrumab prevents semaglutide-induced muscle mass loss in diet-induced obese mice (EASD 2025) - "Bimagrumab prevents semaglutide-induced sarcopenia in DIO mice, implicating activin type II receptors in the adverse effects of weight loss drugs on muscle mass. Bimagrumab may serve as reference compound in DIO mouse and aged-DIO mouse studies aiming to profile potential drug candidates with therapeutic potential to prevent anti-obesity drug-induced sarcopenia."

Preclinical • Metabolic Disorders • Obesity

A Study of LY3985863 in Healthy Participants (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P1 trial

A Study of Bimagrumab (LY3985863) and Tirzepatide (LY3298176), Alone or in Combination, in Participants With Obesity or Overweight With Type 2 Diabetes (clinicaltrials.gov) - P2 | N=180 | Active, not recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Bimagrumab Augments Metabolic Rate to Improve Incretin-Induced Weight Loss in Obese Mice (ADA 2025) - "Hence, targeting the myostatin/activin pathway may provide a greater magnitude and quality weight loss in the management of excess adiposity. The primary objective of the current investigation was to determine whether the ACVR2A/B antagonist mAb bimagrumab provides a greater quality of weight loss when dosed in combination with incretin based multi-receptor agonists in obese mice. A major finding of our studies is that treatment with bimagrumab enhanced GLP-1R agonist and tirzepatide induced weight loss in animals housed at thermoneutrality, while there was no effect of a neutralizing mAb targeting myostatin. Collectively, our findings provide further support to the notion that inhibition of the myostatin/activin pathway in adipose tissue may promote a greater quality of weight loss in the management of excess adiposity."

Late-breaking abstract • Preclinical • Metabolic Disorders • Obesity • ACVR2A • TGFB1

Activin Pathway Inhibition in Adipose Tissue and Muscle—The Bimagrumab Story (ADA 2025) - No abstract available

Metabolic Disorders

Symposium - Can We Improve the Quality of Weight Loss by Augmenting Fat Mass Loss while Preserving Lean Mass? The BELIEVE Study of Bimagrumab + Semaglutide (ADA 2025) - No abstract available

Metabolic Disorders

BELIEVE Study Design—A Multinational, Double-Blind, Placebo-Controlled, Phase 2 Study of Bimagrumab and/or Semaglutide in People with Obesity/Overweight without Diabetes (ADA 2025) - No abstract available

Clinical • P2 data • Diabetes • Metabolic Disorders • Obesity

Bimagrumab + Semaglutide Highly Effective for Loss of Fat, Preservation of Muscle in Phase 2b BELIEVE Trial (Patient Care) - P2 | N=507 | BELIEVE (NCT05616013) | Sponsor: Eli Lilly and Company | "In the Phase 2b BELIEVE trial, participants receiving a combination of bimagrumab, a monoclonal antibody that promotes muscle growth, and semaglutide experienced a significantly higher proportion of fat loss compared to those receiving either drug alone. Of the total body weight lost in the combination group, 92.8% was from fat mass, compared to 71.8% in the semaglutide-alone group. The combination resulted in a 22.1% overall weight reduction, compared to −10.8% for bimagrumab alone and −15.7% for semaglutide alone. Treatment with bimagrumab alone led to 100% of weight loss attributable to fat mass, along with a 2.5% gain in total lean mass."

P2b data • Obesity

Bimagrumab and sarcopenia. (PubMed, Aging Clin Exp Res) - No abstract available

Journal • Sarcopenia

Lilly announces details of presentations at American Diabetes Association's (ADA) 85th Scientific Sessions (Eli Lilly Press Release) - "Eli Lilly and Company...announced that data from studies of...tirzepatide (Zepbound and Mounjaro), retatrutide, eloralintide and bimagrumab will be presented at the American Diabetes Association's (ADA) 85th Scientific Sessions taking place June 20-23 in Chicago."

Clinical data • Preclinical • Obesity

Current and Emerging Parenteral and Peroral Medications for Weight Loss: A Narrative Review. (PubMed, Diseases) - "This narrative review explores established and emerging pharmacotherapies for weight management, including parenteral agents like Liraglutide, Semaglutide, Setmelanotide, and Tirzepatide, as well as peroral medications such as Phentermine, Phentermine/Topiramate, Bupropion/Naltrexone, Orlistat, and Metformin. Newer treatments like Cagrilintide and Bimagrumab show promise for enhancing weight loss outcomes...This includes exploring how AI can complement combination therapies and tailor personalized interventions, thereby grounding its potential benefits in robust clinical evidence. Future directions will focus on integrating AI into clinical trials to refine and personalize obesity management strategies."

Journal • Review • Genetic Disorders • Obesity

Nutrition support whilst on glucagon-like peptide-1 based therapy. Is it necessary? (PubMed, Curr Opin Clin Nutr Metab Care) - "GLP-1 RA therapy for obesity should include resistance training, optimal protein intake and, if needed, specific nutrients and possibly pharmacological interventions to preserve muscle mass. Further research is needed to assess the long-term effects of GLP-1 RA on muscle health and to refine strategies to prevent sarcopenia in patients undergoing pharmacological weight loss."

Journal • Genetic Disorders • Obesity • Sarcopenia • ACVR2A

New drugs for the treatment of obesity: do we need approaches to preserve muscle mass? (PubMed, Rev Endocr Metab Disord) - "Of weight lost with semaglutide, approximately 45% is from lean mass, while with tirzepatide, it is 25%...Promising results with bimagrumab are spurring investigaton in this area. For the full potential of disease modification to be achieved, it's a given that we must demonstrate safe, long term body composition improvement when the new medications are deployed, especially in the older population. This narrative review discusses the justification for focus on lean mass preservation and reviews the status of relevant drugs in development."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Genetic Disorders • Heart Failure • Metabolic Disorders • Nephrology • Obesity • Obstructive Sleep Apnea • Renal Disease • Respiratory Diseases • Sleep Disorder

A Study of Bimagrumab Alone (LY3985863) and Bimagrumab With Tirzepatide (LY900042) in Healthy Participants (clinicaltrials.gov) - P1 | N=100 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Investigate Weight Management with Bimagrumab (LY3985863) and Tirzepatide (LY3298176), Alone or in Combination, in Adults with Obesity or Overweight (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: Eli Lilly and Company | N=140 ➔ 240

Enrollment change • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

A Study of Bimagrumab (LY3985863) and Tirzepatide (LY3298176), Alone or in Combination, in Participants with Obesity or Overweight with Type 2 Diabetes (clinicaltrials.gov) - P2 | N=180 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P2 trial • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

A Study of Bimagrumab Alone (LY3985863) and Bimagrumab With Tirzepatide (LY900042) in Healthy Participants (clinicaltrials.gov) - P1 | N=100 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P1 trial

A Generic Detection Method for the Doping Control Analysis of Fc-Fusion Proteins and Monoclonal Antibodies in Equine Plasma. (PubMed, Drug Test Anal) - "This study is aimed at developing a generic detection method for doping control analysis of nine targeted proteins, each containing the Fc domain of human IgG or IgG from other species in equine plasma, namely, three recombinant Fc-fusion proteins (sotatercept, follistatin-Fc (FST-Fc), and erythropoietin-Fc (EPO-Fc)) and six mAbs (bimagrumab, domagrozumab, garetosmab, landogrozumab, bedinvetmab (Librela), and frunevetmab (Solensia)). The results have demonstrated the method's applicability to equine doping control. This generic method involving affinity purification by Protein A has provided a pragmatic and effective approach to cope with the doping control of novel Fc domain-containing proteins."

Journal • ACVR2A

The Effect of Anti-Activin Receptor Type IIA and Type IIB Antibody on Muscle, Bone and Blood in Healthy and Osteosarcopenic Mice. (PubMed, J Cachexia Sarcopenia Muscle) - "Treatment with αActRIIA/IIB ab caused a significant increase in both skeletal muscle mass and bone parameters in both healthy and immobilized mice, suggesting a potential in the treatment of concurrent osteopenia and sarcopenia. Interestingly, the bone anabolic effect of the treatment was much more pronounced on trabecular bone than on cortical bone. There was no pronounced effect of short-term treatment on haematopoiesis."

Journal • Preclinical • Cardiovascular • Hematological Disorders • Osteoporosis • Rheumatology • Sarcopenia • ACVR2A • SMAD2

Efficacy and safety of pharmacological treatments in inclusion body myositis: a systematic review. (PubMed, RMD Open) - "Drug interventions for IBM were not effective for most of the outcomes of interest. We observed inconsistency of outcome measures across trials. More RCTs are needed, of adequate size and duration, and using a standardised set of outcome measures."

Clinical • Journal • Review • CNS Disorders • Immunology • Myositis

A Study to Investigate Weight Management With Bimagrumab (LY3985863) and Tirzepatide (LY3298176), Alone or in Combination, in Adults With Obesity or Overweight (clinicaltrials.gov) - P2 | N=140 | Recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Apr 2026 ➔ Nov 2026 | Trial primary completion date: Oct 2025 ➔ Feb 2026

Trial completion date • Trial primary completion date • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus