FDA Approves Scholar Rock's Isembyld, First SMA Therapy Aimed at Muscle Loss

The U.S. Food and Drug Administration on September 11 approved Scholar Rock's Isembyld (apitegromab-mstn) injection to treat spinal muscular atrophy (SMA) in adults and children 2 years of age and older who are already receiving an SMN2-targeted treatment, the agency announced. The FDA said Isembyld is the first therapy approved for SMA that directly targets muscle loss.

The decision is the first regulatory approval for the company, as reported by Reuters, via KSL. The company said Isembyld will be available in the coming days, according to that report.

How the drug works

SMA is caused by a faulty SMN1 gene that fails to produce a protein motor neurons need to survive, leading to progressive muscle weakness and wasting, the FDA said. Existing therapies act on a backup gene, SMN2, so the body can make more of the missing protein. The agency said patients with more advanced disease still have substantial motor limitations on those treatments.

Isembyld is a monoclonal antibody that blocks the activation of myostatin, a protein that limits muscle growth, with the aim of increasing muscle mass and strength, according to the Reuters report. It is given by intravenous infusion once every four weeks alongside an SMN2-targeted therapy.

The Phase 3 trial

The FDA said the approval rests on a 52-week randomized, double-blind, placebo-controlled trial (NCT05156320), the Phase 3 trial known as SAPPHIRE. It enrolled 188 participants aged 2 to 21 who could not walk or move independently, all already on an approved SMN2-targeted treatment. They received Isembyld at 10 mg/kg, Isembyld at 20 mg/kg, or placebo. The primary analysis covered 156 patients aged 2 to 12.

On the Hammersmith Functional Motor Scale Expanded, patients in that age group on the 10 mg/kg dose showed a significant difference from placebo, with treated patients improving over a year while those on placebo declined, the agency said. Those on Isembyld were more than twice as likely to show a clinically meaningful improvement: 34.2% versus 13.5%.

The most common adverse reactions were upper respiratory tract infections, vomiting, cough, other viral infections, headache, gastroenteritis and sore throat. The FDA said an increased risk of fractures, including serious fractures, was observed in patients treated with Isembyld, and that the drug may cause fetal harm and may affect reproductive function.

Isembyld received Fast Track, Orphan Drug and Rare Pediatric Disease designations.

A second attempt

The FDA rejected Scholar Rock's first application in 2025 without noting issues specific to the therapy, after concerns were raised during an inspection of Catalent Indiana, a third-party fill-finish facility, SMA News Today reported in April. The company resubmitted with a second U.S.-based fill-finish facility included in the application, and expected a decision by late September, according to that report.

Isembyld will compete with Biogen's Spinraza, Novartis' gene therapy Zolgensma and Roche's oral Evrysdi, Reuters reported. Scholar Rock is also testing the drug to preserve muscle in people with obesity, and a separate trial called OPAL is testing it in babies and toddlers up to age 2.