The US Food and Drug Administration has approved apitegromab-mstn (Isembyld) for spinal muscular atrophy in adult and pediatric patients aged 2 years and older who are receiving survival motor neuron 2-targeted treatment, according to a Scholar Rock press release. 

Spinal muscular atrophy (SMA) is a genetic neuromuscular disease characterized by irreversible motor neuron loss, atrophy of voluntary muscles of the limbs and trunk, and progressive muscle wasting. Apitegromab is a fully human monoclonal immunoglobulin G4 antibody designed to inhibit myostatin signaling through binding to promyostatin and latent myostatin.

The approval was based on results from SAPPHIRE, a phase 3 randomized, double-blind, placebo-controlled trial that evaluated apitegromab in 188 patients aged 2 to 21 years with 5q SMA across 9 countries. All patients were receiving background treatment with nusinersen or risdiplam.

Patients were randomly assigned 1:1:1 to receive intravenous apitegromab 20 mg/kg, apitegromab 10 mg/kg, or placebo every 4 weeks for approximately 1 year. The recommended dosage of apitegromab is 10 mg/kg.

The main efficacy population included 103 patients aged 2 to 12 years. At 1 year, patients receiving apitegromab 10 mg/kg plus survival motor neuron 2-targeted treatment had a 2.2-point improvement on the Hammersmith Functional Motor Scale-Expanded compared with patients receiving survival motor neuron 2-targeted treatment alone. An improvement of at least 3 points occurred in 34% of patients receiving apitegromab compared with 14% receiving placebo.

The apitegromab safety database includes more than 500 patients across clinical studies, some of whom have received treatment for more than 7 years. In SAPPHIRE, the most common adverse reactions were upper respiratory tract infections, vomiting, cough, viral infections, headache, gastroenteritis, pharyngitis, and hypersensitivity. Fractures occurred in 9% of patients receiving apitegromab 10 mg/kg vs 2% receiving placebo.

Following the approval, the FDA awarded Scholar Rock a Rare Pediatric Disease Priority Review Voucher.

Source: Scholar Rock