FDA approves Isembyld, first spinal muscular atrophy therapy to directly target muscle loss

On September 11, 2026, FDA approved Isembyld (apitegromab-mstn) for adults and children aged 2 years or older with spinal muscular atrophy (SMA) who are already receiving survival motor neuron 2 (SMN2)-directed treatment. Isembyld is the first approved therapy for the disease that acts directly on muscle.

Spinal muscular atrophy is a rare inherited neuromuscular disease caused by a faulty SMN1 gene, leading to irreversible motor neuron loss, progressive muscle weakness, and wasting. Existing disease-modifying treatments increase the amount of functional survival motor neuron protein produced by SMN2, a related gene that can partially compensate for the SMN1 defect. These treatments help preserve motor neurons and have substantially improved outcomes, but many patients continue to have significant weakness and functional limitations. Isembyld complements them by inhibiting myostatin, a protein that limits muscle growth.

Isembyld approval was based on the 52-week, randomized, placebo-controlled phase 3 SAPPHIRE trial, which enrolled 188 nonambulatory patients aged 2 to 21 years across nine countries. All participants continued background treatment with one of the two established SMN2-directed therapies, nusinersen or risdiplam.

In the primary efficacy population of 103 patients aged 2 to 12 years, the recommended 10 mg/kg dose produced a statistically significant 2.2 point advantage over placebo after 52 weeks on the Hammersmith Functional Motor Scale–Expanded. The 66 point scale evaluates 33 abilities, including sitting, rolling, kneeling, standing, and climbing stairs, with higher scores indicating better motor function.

To put the average difference into clinical context, a gain of at least 3 points was considered clinically meaningful. That threshold was reached by 34.2% of patients receiving Isembyld versus 13.5% receiving placebo. Overall, motor function improved with Isembyld while declining with background therapy alone.

Isembyld is administered by intravenous infusion every four weeks. Common adverse reactions included respiratory and other viral infections, vomiting, cough, headache, gastroenteritis, pharyngitis, and hypersensitivity. Fractures occurred in 9% of patients receiving the recommended dose versus 2% with placebo and included serious fractures. Isembyld may also cause fetal harm and affect reproductive function.

“Today’s approval of Isembyld marks a new era for the treatment of SMA,” said Basil Darras, MD, principal investigator and director of the Neuromuscular Center and Spinal Muscular Atrophy Program at Boston Children’s Hospital. “As neurologists, families consistently tell us that their top priority is gaining motor function, and we are now able to directly target the muscle, not just the motor neuron, for people living with SMA.”

Sources: FDA. (2026 Sep 11) FDA approves first therapy to target muscle loss in spinal muscular atrophy; Scholar Rock. (2026 Sep 11) Scholar Rock announces FDA approval of Isembyld (apitegromab-mstn), the first and only muscle-targeted treatment for children and adults with spinal muscular atrophy