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

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

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

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

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

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

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 | Not yet recruiting ➔ Recruiting

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

Bimagrumab Prevents Semaglutide-Induced Muscle Mass Loss in Diet-Induced Obese Mice (OBESITY WEEK 2024) - "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 studies aiming to profile potential drug candidates with therapeutic potential to prevent anti-obesity drug-induced sarcopenia."

Preclinical • Genetic Disorders • Obesity • Sarcopenia

Simultaneous detection of myostatin-targeting monoclonal antibodies in dried blood spots and plasma using liquid chromatography-tandem mass spectrometry with field asymmetric ion mobility spectrometry. (PubMed, J Pharm Biomed Anal) - "In this study, we aimed to develop and validate a multitarget method to detect the prohibited transforming growth factor-β superfamily-targeting monoclonal antibodies, such as landogrozumab, domagrozumab, and the activin receptor type IIB-targeting antibody, bimagrumab, in human plasma and dried blood spot (DBS) samples using liquid chromatography-tandem mass spectrometry. Recovery was 31.6-49.8 % for DBS and 51.4-85.3 % for plasma, with no significant matrix effect. This study provides an effective method for doping analysis and novel protein detection."

Journal

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 | Not yet recruiting | Sponsor: Eli Lilly and Company

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

Bimagrumab: an investigational human monoclonal antibody against activin type II receptors for treating obesity. (PubMed, J Basic Clin Physiol Pharmacol) - "However, it is essential to note that Bimagrumab also blocks the effects of other ActRII ligands, which play a role in the neurohormonal axes, pituitary, gonads, and adrenal glands. These observations suggest that bimagrumab might represent a new approach for treating patients with obesity and related metabolic disturbances."

Clinical • Journal • Review • Diabetes • Genetic Disorders • Metabolic Disorders • Musculoskeletal Diseases • Obesity • Orthopedics • Sarcopenia • Type 2 Diabetes Mellitus • ACVR2A

Effect of Bimagrumab on body composition: a systematic review and meta-analysis. (PubMed, Aging Clin Exp Res) - "This meta-analysis provides valuable insights into the effects of bimagrumab on sarcopenic patients, highlighting its significant improvements in body composition parameters but limited impact on functional outcomes. The observed heterogeneity in outcomes across studies underscores the need for cautious interpretation, considering variations in study populations, treatment durations, and outcome assessments. While bimagrumab shows promise as a safe pharmacological intervention for enhancing muscle mass and reducing fat mass in sarcopenia, its minimal effects on muscle strength and broader physical performance suggest potential limitations in translating body composition improvements into functional gains. Further research is needed to clarify its long-term efficacy, optimal dosing regimens, and potential benefits for specific subgroups of sarcopenic patients."

Clinical • Journal • Retrospective data • Review • Muscular Atrophy • Sarcopenia

EFFICACY OF PHARMACOLOGICAL TREATMENT IN INCLUSION BODY MYOSITIS: A SYSTEMATIC REVIEW (EULAR 2024) - "Trials of methotrexate (MTX), intravenous immunoglobulin, interferon beta-1a and MTX, MTX and anti-T-lymphocyte Immunoglobulin, oxandrolone, MTX and azathioprine, bimagrumab, arimoclomol, and sirolimus provided low to high-quality evidence of having no effect on the progression of IBM. Drug interventions for IBM were not effective for most of the outcomes of interest. We observed inconsistency of outcome measures across trials. More randomized controlled trials are needed, of adequate size and duration, and using a standardized set of outcome measures."

Clinical • Review • CNS Disorders • Immunology • Muscular Atrophy • Myositis

Effect of Bimagrumab on Body Composition, Insulin Sensitivity, and Bone in Adults With Obesity (clinicaltrials.gov) - P2 | N=65 | Not yet recruiting | Sponsor: Massachusetts General Hospital | Trial completion date: Jul 2027 ➔ Aug 2028 | Initiation date: Oct 2023 ➔ Jul 2024 | Trial primary completion date: Jul 2027 ➔ Aug 2028

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

What is the pipeline for future medications for obesity? (PubMed, Int J Obes (Lond)) - "Other combinations of entero-pancreatic hormones including cagrisema (GLP-1/amylin RA) and the triple agonist retatrutide (GLP-1/GIP/glucagon RA) have also progressed to phase 3 trials as obesity treatments and early data suggests that may lead to even greater WL than tirzepatide. Additionally, agents with different mechanisms of action to entero-pancreatic hormones (e.g. bimagrumab) may improve the body composition during WL and are in early phase clinical trials. We are in a new era for obesity pharmacotherapy where combinations of entero-pancreatic hormones approach the WL achieved with bariatric surgery. In this review, we present the efficacy and safety data for the pipeline of obesity pharmacotherapies with a focus on entero-pancreatic hormone-based treatments and we consider the clinical implications and challenges that the new era in obesity management may bring."

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

Antibody Blockade of Activin Type II Receptors Preserves Skeletal Muscle Mass and Enhances Fat Loss During GLP-1 Receptor Agonism. (PubMed, Mol Metab) - "Collectively, these data demonstrate that blockade of ActRII signaling improves body composition and metabolic parameters during calorie deficit driven by GLP-1 receptor agonism and demonstrate the existence of Akt-independent pathways supporting muscle hypertrophy in the absence of ActRII signaling."

Journal • Genetic Disorders • Obesity • ACVR2A • TGFB1

Safety and Efficacy of Bimagrumab and Semaglutide in Adults Who Are Overweight or Obese (clinicaltrials.gov) - P2 | N=507 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial primary completion date: Sep 2025 ➔ May 2024

Trial primary completion date • Genetic Disorders • Obesity

Bimagrumab prevents muscle loss associated with low dietary protein intake in healthy volunteers or with weight loss in obesity (EASD 2023) - "Bimagrumab as a single i.v. dose of 3 or 10 mg/kg increased TMV (MRI) at Day 29 in healthy adults on a normal or high protein diet and prevented TMV loss on a low protein diet, in contrast to placebo group. In persons with obesity and T2DM, bimagrumab decreased fat mass and increased lean mass despite minimal change in total caloric intake. These data suggest that bimagrumab's muscle anabolic effects could mitigate lean mass loss associated with decreased protein intake due to dieting and other weight loss interventions."

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

Effect of Bimagrumab on Body Composition, Insulin Sensitivity, and Bone in Adults With Obesity (clinicaltrials.gov) - P2 | N=65 | Not yet recruiting | Sponsor: Massachusetts General Hospital

New P2 trial • Genetic Disorders • Obesity