FDA Approves Apitegromab-mstn, First Muscle-Targeted SMA Therapy

The FDA has approved apitegromab-mstn (Isembyld; Scholar Rock, Inc), the first therapy for spinal muscular atrophy (SMA) that directly targets muscle loss rather than the underlying motor neuron defect. The approval was announced in a news release by the FDA.¹

Cleared for adults and pediatric patients aged 2 and older who are already receiving an SMN2-targeted treatment, apitegromab gives pharmacists a new adjunctive option for patients who continue to experience motor deficits despite existing therapy. The key pharmacist framing is that this drug works alongside—not in place of—nusinersen (Spinraza; Ionis Pharmaceuticals) or risdiplam (Evrysdi; Genentech, Roche), addressing a dimension of the disease those agents leave unmet.¹

A New Mechanism Layered Onto Existing Care

SMA is a rare, progressive neuromuscular disease affecting approximately 1 in 10,000 live births and is among the leading genetic causes of infant mortality, caused by a faulty SMN1 gene that fails to produce a protein essential for motor neuron survival. Existing SMN2-targeted therapies correct that defect so the body can produce enough of the missing protein to keep motor neurons alive, but patients with more advanced disease continue to experience substantial motor limitations.^1,2

Apitegromab is a fully human monoclonal antibody that selectively inhibits myostatin activation, aiming to improve muscle function directly.^1,2

What the SAPPHIRE Trial Showed

Effectiveness was evaluated in SAPPHIRE, a 52-week, double-blind, placebo-controlled phase 3 trial (NCT05156320) that enrolled 188 nonambulatory patients aged 2 to 21 years with type 2 or type 3 SMA, all already receiving nusinersen or risdiplam. Patients were randomly assigned to apitegromab 10 mg/kg, apitegromab 20 mg/kg, or placebo via intravenous infusion every 4 weeks. The primary analysis was conducted in the 156 patients aged 2 to 12 years.^1-4

The primary end point was change from baseline in the Hammersmith Functional Motor Scale-Expanded (HFMSE) at 12 months. Among patients aged 2 to 12 years, the combined apitegromab groups showed a least squares mean difference of 1.8 points versus placebo (95% CI, 0.30-3.32; P = .019), with treated patients improving while those on placebo declined.^1-3

The FDA noted that patients in the treatment arm were more than twice as likely as those on placebo to achieve a clinically meaningful improvement (34.2% vs 13.5%). Notably, the 20 mg/kg dose alone did not reach statistical significance against placebo (least squares mean difference, 1.4; 95% CI, −0.34 to 3.13; P = .11).^2,3

Safety and Dispensing Considerations

In SAPPHIRE, adverse event incidence and severity were similar between apitegromab and placebo, and no patients discontinued because of adverse events. The most common adverse reactions in the FDA labeling were upper respiratory tract infections, vomiting, cough, other viral infections, headache, gastroenteritis, and pharyngitis.^1-3

Pharmacists should be aware of 2 labeled risks that did not dominate the trial's tolerability picture but warrant counseling: an increased risk of fractures, including serious fractures, and the potential for fetal harm and effects on reproductive function.^1-3

Apitegromab previously received Fast Track, Orphan Drug, and Rare Pediatric Disease designations.⁵

REFERENCES

1. FDA approves first therapy to target muscle loss in spinal muscular atrophy. FDA. News release. Released September 11, 2026. Accessed September 14, 2026. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-therapy-target-muscle-loss-spinal-muscular-atrophy

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, randomized, placebo-controlled trial. Lancet Neurol. 2025;24(9):727-739. doi:10.1016/S1474-4422(25)00225-X

3. Halpern L. Study: Apitegromab meaningfully improves motor function in spinal muscular atrophy. Pharmacy Times. Published August 29, 2025. Accessed September 14, 2026. https://www.pharmacytimes.com/view/study-apitegromab-meaningfully-improves-motor-function-in-spinal-muscular-atrophy

4. 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. ClinicalTrials.gov Identifier: NCT05156320. Last Updated January 22, 2026. Accessed September 14, 2026. https://clinicaltrials.gov/study/NCT05156320

5. Gallagher A. Scholar Rock submits FDA application for apitegromab to improve motor function in spinal muscular atrophy. Pharmacy Times. Published January 30, 2026. Accessed September 14, 2026. https://www.pharmacytimes.com/view/scholar-rock-submits-fda-application-for-apitegromab-to-improve-motor-function-in-spinal-muscular-atrophy