FDA Approval

FDA Approves Isembyld as First Spinal Muscular Atrophy Therapy Targeting Muscle Loss

Edited by:
Anthony Calabro, MA

Key Highlights

  • The approval covers adults and children aged 2 years or older receiving an SMN2-targeted treatment.
  • Apitegromab-mstn is the first approved SMA therapy that directly targets muscle loss.
  • Clinically meaningful motor improvement occurred in 34.2% of treated patients versus 13.5% receiving placebo.
  • An increased risk of fractures, including serious fractures, was observed.

On September 11, the FDA approved apitegromab-mstn injection (Isembyld; Scholar Rock) for adults and pediatric patients aged 2 years or older with spinal muscular atrophy (SMA) who are receiving an SMN2-targeted treatment. Apitegromab-mstn is the first SMA therapy approved to directly target muscle loss, complementing treatments that address insufficient survival motor neuron protein production.

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. A faulty SMN1 gene does not produce sufficient protein to sustain motor neuron survival, resulting in progressive muscle weakness and wasting. Existing therapies target the backup SMN2 gene to increase production of the missing protein. Despite improved outcomes with these treatments, patients with more advanced disease may continue to experience substantial motor limitations.

Effectiveness and safety were evaluated in a 52-week randomized, double-blind, placebo-controlled trial (NCT05156320) involving 188 patients aged 2 to 21 years who could not move or walk independently. Participants received apitegromab-mstn 10 mg/kg, apitegromab-mstn 20 mg/kg, or placebo by intravenous infusion every 4 weeks while continuing SMN2-targeted therapy.

The primary analysis included 156 patients aged 2 to 12 years. At 1 year, the 10-mg/kg group improved on the Hammersmith Functional Motor Scale Expanded while the placebo group declined. Clinically meaningful improvement occurred in 34.2% and 13.5% of patients, respectively.

The most common adverse reactions were upper respiratory tract infections, vomiting, cough, other viral infections, headache, gastroenteritis, and pharyngitis. The FDA also reported an increased risk of fractures, including serious fractures, as well as the potential for fetal harm and effects on reproductive function.

Trial regimens consisted of 10 or 20 mg/kg administered intravenously every 4 weeks for approximately 1 year.

Reference
US Food and Drug Administration. FDA approves first therapy to target muscle loss in spinal muscular atrophy. Accessed September 15, 2026. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-therapy-target-muscle-loss-spinal-muscular-atrophy