Regulatory & Policy

US FDA approves Scholar Rock’s Isembyld as first muscle-targeted SMA therapy

Edited by Robert McTiernan··2 min read
US FDA approves Scholar Rock’s Isembyld as first muscle-targeted SMA therapy

The US FDA has approved Isembyld (apitegromab-mstn) for spinal muscular atrophy (SMA) in adults and children aged two years and older who are currently receiving a survival motor neuron 2 (SMN2)-targeted treatment. The approval, granted to Cambridge, Massachusetts-based Scholar Rock (Nasdaq: SRRK), introduces a muscle-directed mechanism to a treatment landscape that has until now focused on motor neuron preservation.

Isembyld is administered as an intravenous infusion at 10 mg/kg once every four weeks. It is a fully human monoclonal IgG4 antibody that binds to promyostatin and latent myostatin, blocking myostatin activation and thereby inhibiting the signaling pathway that suppresses muscle growth. Unlike SMN2-targeted therapies such as nusinersen (Spinraza) and risdiplam (Evrysdi), Isembyld acts directly on muscle and is intended to be used alongside existing disease-modifying treatment.

The approval was based on the Phase III SAPPHIRE trial (NCT05156320), which enrolled 188 patients aged 2–21 years with 5q SMA receiving background SMN2-targeted therapy. In the primary efficacy population of patients aged 2–12 years (n=103), Isembyld produced a 2.2-point treatment difference versus placebo on the Hammersmith Functional Motor Scale-Expanded at one year (nominal p=0.0121). The US label is broader than the pivotal efficacy population, covering adults and children aged two years and older who are receiving an SMN2-targeted therapy.

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Scholar Rock was also awarded a Rare Pediatric Disease Priority Review Voucher with the approval.

The SMA treatment landscape has expanded considerably since the first SMN-targeted approvals, with Biogen's high-dose Spinraza regimen receiving FDA clearance and Novartis's gene therapy Itvisma (onasemnogene abeparvovec) now approved in older patients in Europe. Roche discontinued its myostatin inhibitor emugrobart in SMA after lackluster findings, leaving Scholar Rock as the only company to reach approval with a muscle-targeted agent in this setting. Scholar Rock said it has previously navigated manufacturing complications during the regulatory process, which involved removing the Catalent Indiana fill-finish site from the US BLA under FDA guidance and proceeding with an alternate facility. In Europe, Scholar Rock withdrew the MAA and plans to resubmit with the alternate facility.

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