Scholar Rock, a biopharmaceutical company focused on developing innovative treatments, has announced the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for apitegromab. This muscle-targeted therapy is intended to improve motor function in individuals with spinal muscular atrophy (SMA) who are already receiving survival motor neuron (SMN)-targeted treatments.
The BLA submission is supported by data from the Phase 3 SAPPHIRE trial and the Phase 2 TOPAZ study. Scholar Rock has requested priority review from the FDA, which, if granted, would shorten the review time to six months. Apitegromab has previously been granted Fast Track, Orphan Drug, and Rare Pediatric Disease designations by the FDA, along with PRIME and Orphan Medicinal Product designations by the European Medicines Agency (EMA).
SAPPHIRE Trial Results
The Phase 3 SAPPHIRE trial evaluated the safety and efficacy of apitegromab in non-ambulatory patients with Types 2 and 3 SMA who were receiving standard of care treatments, either nusinersen or risdiplam. The trial enrolled 156 patients aged 2-12 years in the main efficacy population, randomized to receive either apitegromab 10 mg/kg, apitegromab 20 mg/kg, or placebo via intravenous infusion every 4 weeks for 12 months. An exploratory population of 32 patients aged 13-21 years was also evaluated.
The SAPPHIRE trial met its primary endpoint, demonstrating a statistically significant 1.8-point improvement in the Hammersmith Functional Motor Scale-Expanded (HFMSE) for patients receiving apitegromab compared to placebo at week 52. Further analysis showed that patients receiving apitegromab 10 mg/kg had a mean HFMSE improvement of 2.2 points compared to placebo (nominal P = 0.0121).
Future Plans for Apitegromab
Scholar Rock plans to initiate the Phase 2 OPAL trial in mid-2025 to study apitegromab in SMA patients under two years of age. This trial will evaluate apitegromab in patients who have been or are continuing to be treated with any currently approved SMN therapy, such as nusinersen, risdiplam, or onasemnogene abeparvovec. The company is also expected to file a marketing authorization application to the EMA by the end of the first quarter.
Myostatin Inhibition
Apitegromab is a fully human monoclonal antibody that inhibits myostatin activation by selectively binding the pro- and latent forms of myostatin in skeletal muscle. Myostatin, a member of the TGFβ superfamily of growth factors, is primarily expressed by skeletal muscle cells, and its absence is associated with increased muscle mass and strength. Apitegromab aims to improve motor function in SMA patients by directly targeting muscle.
