Table 1.
Clinical trials of various myostatin-targeting drugs
| Name (type) | Company | Target | Conditions | Phase status | Remark |
|---|---|---|---|---|---|
| MYO-029/Stamulumab (antibody) | Wyeth | MSTN | Healthy, muscular dystrophy (BMD, FSHD, LGMD) | Phase 1 completed (healthy)/Phase 1/2 completed (BMD, FSHD, LGMD) [99] | Development discontinued due to lack of efficacy |
| PF-06252616/Domagrozumab (antibody) | Pfizer | MSTN | Heathy, muscular dystrophy (DMD, LGMD) | Phase 1 completed (healthy) [62]/Phase 2 terminated (DMD)/Phase1/2 completed (LGMD) | Two phase 2 studies (DMD) terminated for lack of efficacy |
| LY-2495655/Landogrozumab (antibody) | Eli Lilly | MSTN | Healthy, cancer cachexia, sarcopenia, elective total hip replacement | Phase 2 completed (healthy, cancer cachexia, sarcopenia, elective total hip replacement) | Lean body mass increased in elderly patients [64]/No efficacy observed in pancreatic cancer [66] |
| REGN-1033/Trevogrumab (antibody) | Regeneron | MSTN | Healthy, sarcopenia | Phase 1 completed (healthy)/Phase 2 completed (sarcopenia) | Efficacy evaluations ongoing |
| SRK-015 (antibody) | Scholar Rock | Pro- and latent MSTN | SMA | Phase 2 active (SMA) | Development ongoing, reduced cross-reactivity with other TGF-β ligands [68] |
| AMG-745/PINTA-745 (peptibody) | Amgen/Atara Biotherapeutics | MSTN | Kidney disease with protein energy wasting | Phase 1/2 completed | Development discontinued due to lack of efficacy |
| RG6206/RO7239361/BMS-986089 (adnectin) | Roche (originally developed by Bristol-Myers) | MSTN | Healthy, DMD | Phase 1 completed (healthy)/Phase 1/2 completed (DMD)/Phase 2/3 active (DMD) | Development discontinued due to lack of efficacy |
| BYM-338/Bimagrumab (antibody) | Novartis | ACVR2A, ACVR2B (has greater affinity for ACVR2B) | sIBM, hip fracture surgery, type 2 diabetes, sarcope- nia, COPD with cachexia, cancer cachexia | Phase 2 completed (Type 2 diabetes, sarcopenia, COPD, cancer cachexia, hip fracture surgery)/Phase 2/3 completed (sIBM) | Development ongoing, thigh muscle volume increased in patients with COPD [78], no efficacy in 6-min walking test observed in phase 2/3 trial in sIBM patients |
| ACE-031/Ramatercept (ACVR2B-Fc) | Acceleron | MSTN, GDF11, Activins, BMPs | Healthy, DMD | Phase 1 completed (healthy)/Phase 2 terminated (DMD) | Study terminated due to serious side effects including nosebleed, gum bleeding, telangiectasia, and/ or erythema [50] |
| ACE-083 (FST291-Fc) | Acceleron | MSTN, GDF11, Activins, BMPs | Healthy, FSHD, CMT | Phase 1 completed (healthy)/Phase 2 terminated (FSHD, CMT) | Study terminated for lack of efficacy in improving muscle function |
| ACE-011/Sotatercept (ACVR2A-Fc) | Acceleron | MSTN, GDF11, Activins, BMPs | Healthy, anemia, osteoporosis, β-thalassemia, PAH, multiple myeloma | Phase 1 completed (healthy)/Phase 2 completed (anemia, multiple myeloma)/Phase 2 active (β-thalassemia, PAH) | Increased RBC number and Hb levels [56,88] |
| ACE-536/Luspatercept (ACVR2B-Fc) | Acceleron | MSTN, GDF11, Activins, BMPs | Healthy, anemia, β-thalassemia | Phase 1 completed (healthy)/Phase 2 completed (anemia, β-thalassemia)/Phase 3 active (anemia, β-thalassemia) [92,100] | Recently approved in the USA for the treatment of anemia associated with β-thalassemia [93] |
| ACE-2494 (Soluble ACVR2B receptor) | Acceleron | MSTN, GDF11, Activins | Healthy, musculoskeletal disorders | Phase 1 completed (healthy) | Development discontinued due to inconsistent anti-drug antibodies profile |
| rAAV1.CMV.huFollistatin344 (FST) | Nationwide Children’s Hospital/Milo Therapeutics | MSTN, GDF11, Activins, BMPs | BMD, sIBM, DMD | Phase 1 completed (BMD, sIBM) [84,85]/Phase 1/2 completed (DMD) | Development ongoing |
MSTN, myostatin; ACVR2A, activin type 2A receptor; ACVR2B, activin type 2B receptor; GDF11, growth differentiation factor 11; BMP, bone morphogenetic protein; BMD, Becker muscular dystrophy; FSHD, facioscapulohumeral muscular dystrophy; LGMD, limb-girdle muscular dystrophy; DMD, Duchenne muscular dystrophy; SMA, spinal muscular atrophy; sIBM, sporadic inclusion body myositis; COPD, chronic obstructive pulmonary disease; CMT, Charcot-Marie-Tooth disease; PAH, pulmonary arterial hypertension; TGF-β, transforming growth factor-β; RBC, red blood cell; Hb, hemoglobin.