Table 1.

Clinical trials testing anti-myostatin antibodies in neuromuscular disorders

Intervention	Comp	Company name	TID/MoA	Trial phase	Disease	Patients enrolled	Inclusion criteria	Delivery route	Primary outcome	Main result	Current stage	Clinical trial number	Ref
RO7204239 (GYM329)	Anti-MSTN mAb	Hoffmann-La Roche	Binding of pro-MSTN	II-III	SMA	NA (est. 180)	Symptomatic, genetic diagnosis of 5q SMA, 2–10 years, ambulant, risdiplam treatment	SUB	Safety, tolerability, pharmacokinetics, pharmacodynamics, efficacy	NA	Not yet recruiting	NCT05115110	NA
SRK-015 (apitegromab)	Anti-propeptide mAb (IgG4/ lambda isotype)	Scholar Rock, Inc	Binding of pro-MSTN	II	SMA	58	5–21 (Cohorts 1–2) and ≥ 2 (Cohort 3) years, genetic diagnosis of 5q SMA, ambulant or non-ambulant but able to sit independently	IV	Efficacy	NA	Active, not recruiting	NCT03921528	NA
SRK-015 (apitegromab)	Anti-propeptide mAb (IgG4/ lambda isotype)	Scholar Rock, Inc	Binding of pro-MSTN	III	SMA	204	2–21 years, genetic diagnosis of 5q SMA, diagnosis of later-onset SMA before receiving nusinersen or risdiplam, non-ambulant, having received nusinersen for 10 months or risdiplam for 6 months before screening, HFMSE ≥ 10 and ≤ 45	IV	Efficacy, safety	NA	Not yet recruiting	NCT05156320	NA
PF-06252616 (domagrozumab)	Anti-MSTN mAb	Pfizer	Binding of ActRII	II	DMD	121	6–15 years, diagnosis of DMD, ambulant, stable glucocorticoid treatment	IV	Safety, pharmacokinetics, pharmacodynamics, efficacy	Treatment-emergent AEs: 115 Serious AEs: 6 (not drug-related) No change in 4SC time from baseline	Terminated	NCT02310763	Wagner et al., [104, 111]
PF-06252616 (domagrozumab)	Anti-MSTN mAb	Pfizer	Binding of ActRII	II	DMD	59	6–18 years, diagnosis of DMD, completed study B5161002, GLDH < 20 UI/L, normal hepatic function, normal estimated hepatic iron content on liver MRI	IV	Long term safety, pharmacodynamics, pharmacokinetics, efficacy	Treatment-emergent AEs: 59 Sever AEs: 4 (1 died of fat embolism from tibial fracture) Serious AEs: 8 (not drug-related) No change in 4SC time from baseline	Terminated	NCT02907619	Wagner et al., [104, 111]
RO7239361 (BMS-986089, taldefgrobep alfa)	Anti-MSTN adnectin	Hoffmann-La Roche	Binding of MSTN	I-II	DMD	43	5–10 years, diagnosis of DMD, able to walk without assistance and to walk up 4 stairs in ≤ 8 s, weight ≤ 15 kg, glucocorticoid treatment	SUB	Safety, tolerability, pharmacokinetics	NA	Terminated	NCT02515669	NA
RO7239361 (BMS-986089, taldefgrobep alfa)	Anti-MSTN adnectin	Hoffmann-La Roche	Binding of MSTN	II-III	DMD	166	6–11 years, diagnosis of DMD, able to walk without assistance and to walk up 4 stairs in ≤ 8 s, NSAA 15, weight ≤ 15 kg, glucocorticoid treatment	SUB	Efficacy, safety, tolerability	NA	Terminated	NCT03039686	NA
ACE-031	Decoy receptor (ActRIIB)	Acceleron Pharma Inc	Binding of MSTN	II	DMD	24	≥ 4 years, diagnosis of DMD, able to walk 10 m in < 12 s, corticosteroid therapy for at least 1 year before enrollment; neck flexors MRC ≤ 4+/5	SUB	Safety, tolerability, pharmacokinetics, pharmacodynamics, efficacy	Treatment-emergent AEs: 7 No serious AEs Trend for improvement in the 6MWT distance in the treatment groups	Terminated	NCT01099761; NCT01239758	Campbell et al., [114]
MYO-029	Anti-MSTN mAb	Wyeth (Pfizer)	Binding of MSTN	I-II	BMD, FSHD, LGMD	116	≥ 18 years, diagnosis of BMD, FSHD or LGMD (2A, 2B, 2C, 2D, 2E, 2I), able to walk without assistance, MRC ≥ 3 − and ≤ 4 + in at least 8 of 16 muscle groups, FVC ≥ 60% of the predicted value, ejection fraction > 40%	IV	Safety, tolerability, efficacy	Treatment-emergent AEs: 104 (only accidental injury significantly higher in the treatment groups) No improvement in muscle strength	Completed	NCT00104078	Wagner et al., [103]
PF-06252616 (domagrozumab)	Anti-MSTN mAb	Kathryn Wagner (and Pfizer)	Binding of ActRII	Ib-II	LGMD-2I	19	18–99 years, diagnosis of LGMD2I, able to walk, run, rise from chair, normal hepatic and renal function, normal estimated hepatic iron content on liver MRI	IV	Safety, tolerability, pharmacokinetics, pharmacodynamics, efficacy	NA	Completed	NCT02841267	NA
Bimagrumab (BYM338)	Anti-receptor mAb	Novartis Pharmaceuticals	Binding of ActRII	II	IBM	14	40–80 years, diagnosis of IBM, able to walk ≥ 3 m without assistance	IV	Safety, tolerability, efficacy	Treatment-emergent AEs: 13 No serious AEs Increased thigh muscle volume, LBM, improvement in 6MWT distance in treatment group	Completed	NCT01423110	Amato et al., [112]
Bimagrumab (BYM338)	Anti-receptor mAb	Novartis Pharmaceuticals	Binding of ActRII	II-III	IBM	251	36–85 years, diagnosis of IBM, able to walk without assistance	IV	Safety, tolerability, efficacy	Treatment-emergent AEs: 250 Serious AEs: 72 Deaths: 2 (not treatment-related) No change in 6MWT distance	Completed	NCT01925209	Hanna et al., [107]
Bimagrumab (BYM338)	Anti-receptor mAb	Novartis Pharmaceuticals	Binding of ActRII	II-III	IBM	10	40–75 years, diagnosis of IBM, participation in the CBYM338X2205 study	IV	Safety, tolerability, efficacy	Treatment-emergent AEs: 10 (3 requiring withdrawn, but not drug-related) Serious AEs: 10 Decline of 6MWT distance from baseline	Completed	NCT02250443	Sivakumar et al., [115]
Bimagrumab (BYM338)	Anti-receptor mAb	Novartis Pharmaceuticals	Binding of ActRII	III	IBM	211	≥ 36 years, diagnosis of IBM, participation in the CBYM338X2205 study	IV	Safety, tolerability, long-term efficacy	Treatment-emergent AEs: 191 Serious AEs: 37 Decline of 6MWT distance from baseline	Completed	NCT02573467	Amato et al., [113]

MSTN myostatin; mAb: monoclonal antibody; Comp compound; est. estimated; SMA spinal muscular atrophy; DMD Duchenne muscular dystrophy; BMD Becker muscular dystrophy; FSHD facioscapulohumeral dystrophy; LGMD-2I limb girdle muscle dystrophy type 2I; IBM inclusion body myositis; Ig immunoglobulin; FVC forced vital capacity; MRI magnetic resonance imaging; HFMSE Hammersmith Functional Motor Scale Expanded; NSAA North Star Ambulatory Assessment; 4SC 4-stair climb; MRC Medical Research Council; AEs adverse events; LBM lean body mass; NA not available; Ref reference; SUB subcutaneous; IV intravenous; ActRII activin receptor type II