FDA approves apitegromab for children and adults with spinal muscular atrophy

On September 11, 2026, the U.S. Food and Drug Administration (FDA) approved apitegromab for the treatment of spinal muscular atrophy (SMA) in adults and children aged 2 years and older who are currently receiving a survival motor neuron 2 (SMN2)-targeted treatment. The approval introduces the first muscle-targeted treatment for SMA and is based on data from the Phase III SAPPHIRE trial (NCT05156320), in which apitegromab demonstrated a clinically meaningful improvement in motor function compared with placebo.^1,2

Unmet need in spinal muscular atrophy

SMA is a rare, severe neuromuscular disease characterized by irreversible motor neuron loss and progressive muscle wasting, leading to a decline in motor function and loss of independence over time.¹ Although approved SMN2-targeted therapies have substantially improved clinical outcomes for people with SMA, significant motor function deficits can persist. Apitegromab was developed to address this residual impairment by targeting the muscular component of SMA rather than directly modifying SMN production.²

Apitegromab is a fully human monoclonal IgG4 antibody that binds to promyostatin and latent myostatin, inhibiting myostatin activation and blocking myostatin signaling. By targeting this pathway, apitegromab is intended to improve muscle function in individuals with SMA receiving an SMN2-targeted treatment.^1,2

Pivotal data: the Phase III SAPPHIRE trial

The approval was supported by results from SAPPHIRE, a Phase III, double-blind, randomized, placebo-controlled trial evaluating the safety and efficacy of apitegromab in individuals with nonambulatory type 2 or type 3 SMA receiving nusinersen or risdiplam.²

The trial enrolled 188 participants across 48 hospitals in Belgium, France, Germany, Italy, Poland, Spain, the Netherlands, the UK, and the USA. Participants were between 2 and 21 years old, had genetically documented SMN-deficient nonambulatory type 2 or type 3 SMA, and had received at least 10 months of nusinersen or 6 months of risdiplam before screening. Participants aged between 2 and 12 years were randomized to apitegromab 20 mg/kg, apitegromab 10 mg/kg, or placebo every 4 weeks, while participants aged between 13 and 21 years were randomized to apitegromab 20 mg/kg or placebo.² The primary endpoint was the change from baseline in the Hammersmith Functional Motor Scale-Expanded (HFMSE) at 12 months, which was assessed in participants aged between 2 and 12 years who received at least one dose of apitegromab or placebo and had at least one post-baseline evaluable HFMSE assessment (modified intention-to-treat set).²

The study met its primary endpoint, demonstrating a robust, clinically meaningful 2.2-point improvement in the HFMSE in patients receiving apitegromab 10mg/kg and an SMN2-targeted treatment compared with patients receiving an SMN2-targeted treatment alone at one year (nominal p=0.0121).¹ Additionally, 34.2% of patients receiving apitegromab 10 mg/kg achieved a ≥3-point increase in HFMSE compared with 13.5% of those receiving placebo, corresponding to an odds ratio of 3.8 (nominal p=0.0125).¹ The difference between apitegromab 20 mg/kg and placebo was not statistically significant.² 

The safety findings from SAPPHIRE were generally consistent with SMA and background SMA therapy. The incidence and severity of adverse events were similar between apitegromab and placebo, and no patients discontinued treatment because of adverse events.² The most frequently reported adverse events in the trial were pyrexia, nasopharyngitis, cough, vomiting, upper respiratory tract infection, and headache.² Fractures occurred in 9% of patients receiving apitegromab 10 mg/kg compared with 2% of those receiving placebo.¹

Clinical implications

The approval of apitegromab introduces the first muscle-targeted treatment option for children and adults with SMA who are already receiving an SMN2-targeted therapy. The SAPPHIRE findings suggest that inhibiting myostatin activation can provide additional improvements in motor function, with the potential to support greater independence and participation in activities of daily living.^1,2 The approval therefore expands the therapeutic approach to SMA beyond targeting motor neuron survival alone, introducing direct targeting of muscle as a complementary strategy.¹

Written by Hannah Elkheir

Reviewed by Simon Ng

References

1. Scholar Rock. Scholar Rock Announces FDA Approval of ISEMBYLD™ (apitegromab-mstn), the First and Only Muscle-Targeted Treatment for Children and Adults with Spinal Muscular Atrophy (SMA). Available here. (Last accessed: 16/09/2026).
2. Crawford TO, Servais L, Mercuri E, et al. Safety and efficacy of apitegromab in nonambulatory type 2 or type 3 spinal muscular atrophy (SAPPHIRE): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2025;24(9):727–739.