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

Muscle Loss in Obesity Therapy as a Therapeutic Target: Trial Design and Endpoints for Regulatory Discussions. (PubMed, J Cachexia Sarcopenia Muscle) - "Discussions highlighted the impact of glucagon-like peptide-1 (GLP-1) receptor agonists or GLP-1/glucose-dependent insulinotropic polypeptide (i.e., GLP-1/GIP) agonists on body composition and muscle health; the challenges of distinguishing 'true' skeletal muscle from fat-free tissue; the impact of treatment discontinuation and weight regain; advances in imaging and quantitative assessment of lean body mass; as well as insights from emerging muscle-preserving therapies (e.g., bimagrumab, pemvidutide and enobosarm)...These also involve significant regulatory considerations for future drug development and approval pathways, for instance related to the very large number of individuals that may be considered for these therapeutic approaches as well as from the potential long (or life-long) duration of therapy considered with these drugs. Together, these discussions highlight the growing importance of integrating body composition and functional assessments in future..."

Journal • Cachexia • Genetic Disorders • Obesity • Sarcopenia

Risk Factors, Diagnostic Challenges, and Emerging Therapeutic Strategies for ICU-Acquired Weakness: A Brief Review. (PubMed, J Multidiscip Healthc) - "Novel targeted therapies (eg, the myostatin inhibitor Bimagrumab) have demonstrated potential to increase muscle mass in clinical trials...It also underscores the need for future research to focus on developing highly sensitive diagnostic tools, optimizing preventive strategies, and promoting the clinical translation of targeted therapies. Ultimately, this will help establish a comprehensive and precise multi-level intervention framework to improve patient outcomes."

Journal • Review • Critical care • Inflammation • CST3 • MIR451A

Identification of causal plasma proteins and targeted therapy for primary hepatic carcinoma via proteome-wide Mendelian randomization. (PubMed, Commun Biol) - "Complementary druggability profiling prioritized ACVR2B and C1QA as actionable targets. These findings establish the INHBC-ACVR2B axis as a validated pathogenic mechanism in PHC and underscore the potential of repurposing ACVR2B inhibitors (e.g., Bimagrumab) as a precision oncology strategy for PHC management."

Journal • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • ACVR2B • C1QA • TGFB1

Sarcopenia in Aging: Pathogenesis, Diagnosis, and Emerging Therapeutic Frontiers. (PubMed, Mol Imaging Biol) - "Resistance-based exercise and targeted nutritional support remain first-line, but late-phase trials of myostatin-neutralising antibodies (e.g., LY2495655, bimagrumab) and oral selective androgen-receptor modulators (SARMs; e.g., enobosarm, GSK2881078) now show dose-dependent gains in appendicular lean mass and preliminary functional benefits, signalling that combination regimens integrating lifestyle and drug therapy are imminent. Addressing these challenges requires an interdisciplinary strategy that encompasses molecular, clinical, and public health perspectives to mitigate the personal and societal impacts of sarcopenia. Future efforts must focus on harmonizing diagnostic criteria, refining therapeutic regimens, and leveraging emerging technologies to develop targeted interventions that preserve muscle function and enhance quality of life in the aging population."

Journal • Review • Inflammation • Metabolic Disorders • Muscular Atrophy • Sarcopenia

A Study of LY3985863 in Healthy Participants (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

Enrollment closed

Bimagrumab: Novel Medical Therapy for Inclusion Body Myositis, Sarcopenia, and Medication-Induced Lean Body Mass Loss. (PubMed, Cardiol Rev) - "We compare the efficacy of the combination of bimagrumab and semaglutide to a dual incretin glucagon-like peptide-1 receptor agonist and glucose-dependent insulinotropic polypeptide (GIP) drug. Finally, we will show the superiority of bimagrumab to other myostatin inhibitors."

Journal • Diabetes • Genetic Disorders • Immunology • Metabolic Disorders • Musculoskeletal Diseases • Myositis • Obesity • Orthopedics • Sarcopenia • Type 2 Diabetes Mellitus

GenSci156, a Potent Bi-specific Antibody for Obesity Treatment Without Causing Muscle Loss (OBESITY WEEK 2025) - "Bimagrumab is a phase II clinical asset targeting activin type II receptors (ActRII)... We have proved for the first time by blocking ActRIIA/B and GIPR activities can lead to synergistic fat mass loss while preserving muscle mass. GenSci156, which is a bi-specific antibody simultaneously inhibiting signaling pathways of the above two receptors has demonstrated a remarkable fat mass loss while still maintaining weight reduction. Therefore, GenSci156 deserves to be further developed to become a promising treatment option in addition to the current satiety control drugs for high quality weight control."

Genetic Disorders • Obesity • ACVR2A

Bimagrumab Prevents Semaglutide-Induced Muscle Mass Loss in Diet-Induced Obese Mice (OBESITY WEEK 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 • Genetic Disorders • Obesity • Sarcopenia

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

Effect of Tirzepatide and Bimagrumab on Body Composition, Insulin Sensitivity, and Bone in Adults With Obesity (clinicaltrials.gov) - P2 | N=63 | Not yet recruiting | Sponsor: Massachusetts General Hospital | Trial completion date: Jul 2028 ➔ Mar 2029 | Trial primary completion date: Jul 2028 ➔ Dec 2028

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

A Study of Bimagrumab Alone (LY3985863) and Bimagrumab With Tirzepatide (LY900042) in Healthy Participants (clinicaltrials.gov) - P1 | N=125 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

Trial completion

Prevention and intervention against obesity and overweight in the military: a systematic review. (PubMed, J Occup Med Toxicol) - "Effective countermeasure for reducing body weight found in this study were combined interventions, like education on lifestyle changes, dietary habits and promotion of physical activity in military personnel, as well as by ketogenic dietary interventions combined with physical activity and followed by pharmacological intervention approaches. Combined interventions appear promising in some studies, but future evaluations may focus on combinations of physical activity and exercise with new pharmaceutical approaches like Semaglutide or Bimagrumab medication in the long term for military personnel due to probable favorable body composition adaptations and military readiness."

Journal • Review • Genetic Disorders • Obesity

High-fat diet induced obesity and anti-activin receptor antibody: Effects on bone properties in mice. (PubMed, Bone Rep) - "Inhibitors of the activin receptor signaling pathway, such as bimagrumab, an anti-activin receptor antibody (αActRIIA/IIB ab), are under investigation to counteract weight-loss induced muscle loss, but their skeletal effects in obesity remain unclear...Furthermore, αActRIIA/IIB ab improved cortical histological bone formation markers, while morphology remained unaffected, suggesting a site- or time-specific difference. Thus, αActRIIA/IIB ab holds potential for mitigating weight-loss-associated bone deterioration."

Journal • Preclinical • Genetic Disorders • Obesity • ACVR2A

Diabetes reshapes pancreatic cancer-associated endothelial niche by accelerating senescence. (PubMed, Nat Commun) - "Pharmacological inhibition of INHBB receptors with bimagrumab effectively inhibited tumor progression in diabetic mice. Combination treatment with metformin showed synergistic antitumor effects. In conclusion, our study identifies INHBB as a promising therapeutic target for pancreatic cancer with comorbid diabetes, laying the foundation for the development of individualized therapies for pancreatic cancer patients."

Journal • Diabetes • Metabolic Disorders • Oncology • Pancreatic Cancer • Solid Tumor • INHBB • TGFB1

Activin receptor type IIA/IIB blockade increases muscle mass and strength, but compromises glycemic control in mice. (PubMed, Mol Metab) - "Our findings demonstrate that, in accordance with human studies, ActRIIA/IIB blockade holds promise for increasing muscle mass, strength, and muscle insulin sensitivity. However, contrary to the improved glycemic control in humans, ActRIIA/IIB blockade in mice causes severe glucose intolerance and lowers voluntary physical activity. Our study underscores the complex metabolic and functional consequences of ActRIIA/IIB blockade, and highlight species differences on glycemic control, which warrant further investigation."

Journal • Preclinical • Genetic Disorders • Obesity • Oncology • ACVR2A

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 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

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

...bimagrumab is still “currently being studied in an ongoing phase 2 trial with tirzepatide, alone or in combination, in patients with obesity. Results from this trial will be available in 2026.” (FierceBiotech)

P2 data • Obesity

Eli Lilly withdraws phase 2b trial of $1.9B obesity bet before starting enrollment (FierceBiotech) - "The study was designed to test bimagrumab, an asset Lilly acquired in its $1.9 billion Versanis buyout, as a single agent and in combination with blockbuster GLP-1/GIP drug tirzepatide."

Trial withdrawal • 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=0 | Withdrawn | Sponsor: Eli Lilly and Company | N=180 ➔ 0 | Trial completion date: Jan 2027 ➔ Jun 2025 | Active, not recruiting ➔ Withdrawn | Trial primary completion date: Oct 2026 ➔ Jun 2025

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

GenSci156, a potent bi-specific antibody targeting ActRIIA/B and GIPR for obesity treatment without causing muscle loss (EASD 2025) - "Bimagrumab is a phase II clinical asset targeting activin type II receptors (ActRII)... We have proved for the first time by blocking ActRIIA/B and GIPR activities can lead to synergistic fat mass loss while preserving muscle mass. GenSci156, which is a bi-specific antibody simultaneously inhibiting signaling pathways of the above two receptors has demonstrated a remarkable fat mass loss while still maintaining weight reduction. Therefore, GenSci156 deserves to be further developed to become a promising treatment option in addition to the current satiety control drugs for high quality weight control."

Late-breaking abstract • Metabolic Disorders • Obesity • ACVR2A

Weekly PG-102 plus bimagrumab enhances net muscle gain compared to daily semaglutide-based regimens (EASD 2025) - "PG-102 combined with Bimagrumab delivers a synergistic, next-generation obesity therapy that not only reduces fat mass effectively but also preserves—and even increases—lean muscle mass. Remarkably, this was achieved with once-weekly PG-102 dosing, unlike daily Semaglutide-based regimens. These results highlight the added clinical value of GLP-2 receptor engagement and suggest that PG-102 may enhance both muscle function and metabolic quality, supporting its potential to redefine obesity treatment."

Late-breaking abstract • Metabolic Disorders • Obesity • FBXO32

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 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open

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