Apitegromab BLA submitted to FDA for spinal muscular atrophy

Apitegromab BLA submitted to FDA for spinal muscular atrophy | Image Credit: © Araki Illustrations - © Araki Illustrations - stock.adobe.com.

Scholar Rock has submitted a biologics license application (BLA) to the FDA for apitegromab, an investigational muscle-targeted therapy, for the treatment of spinal muscular atrophy (SMA). The submission was supported by data from the phase 3 SAPPHIRE trial and the phase 2 TOPAZ trial, which demonstrated clinically meaningful motor function improvements in patients receiving survival motor neuron (SMN)-targeted treatments.¹

In the SAPPHIRE trial, the primary endpoint was met, showing a statistically significant 1.8-point improvement in the Hammersmith Functional Motor Scale-Expanded (HFMSE) for patients receiving apitegromab compared to placebo at 52 weeks. Scholar Rock requested priority review, which, if granted, would shorten the FDA’s review timeline to 6 months.¹

The trial enrolled 156 patients aged 2 to 12 years in the main efficacy population. Participants received either apitegromab at 10 mg / kg or 20 mg / kg, or a placebo via intravenous infusion every 4 weeks for 12 months. An exploratory population included 32 patients aged 13 to 21 years, who were randomized to receive apitegromab 20 mg / kg or placebo.^1,2

Further analysis of the trial data showed that among patients receiving apitegromab 10 mg / kg, the mean HFMSE improvement was 2.2 points compared to placebo (nominal P = 0.0121). Among those receiving apitegromab 20 mg/kg, the mean difference was 1.4 points (P = 0.1149). Overall, 30.4% of patients receiving apitegromab had a more than 3-point improvement in HFMSE compared to 12.5% in the placebo group.²

"We are gratified that in patients already on a SMN-targeted treatment, the SAPPHIRE trial met its primary endpoint for the main efficacy population showing a statistically significant 1.8-point improvement for patients receiving apitegromab compared to placebo," said Jing Marantz, MD, PhD, chief medical officer at Scholar Rock, in a statement.¹

"With the strength of our Phase 3 data as the foundation of our submission, we look forward to continuing to work closely with the FDA through the review of our BLA on behalf of patients and families living with SMA," said Marantz.¹

Secondary endpoints of the trial included changes in Revised Upper Limb Module scores and other functional assessments. The findings suggested that apitegromab may provide additional motor benefits beyond those achieved with SMN-targeted therapy alone. Patients in both the primary and exploratory populations exhibited numerical trends favoring apitegromab over placebo, reinforcing its potential role in improving mobility outcomes for individuals with SMA, according to Scholar Rock.²

Apitegromab was well tolerated, with no clinically significant differences in adverse events between the 10 mg / kg and 20 mg / kg groups. No serious adverse events were attributed to the drug, and there were no discontinuations due to safety concerns. The most common adverse events reported were mild to moderate and included headache, upper respiratory tract infection, and pyrexia.²

Scholar Rock plans to submit a marketing authorization application to the European Medicines Agency in the first quarter of 2025 and intends to expand the development of apitegromab through the phase 2 OPAL trial. This study, expected to begin in mid-2025, would evaluate apitegromab in SMA patients under 2 years who receive SMN-targeted therapy. The expansion of the clinical program underscores Scholar Rock’s commitment to addressing unmet needs in SMA treatment across a broad range of patient populations.¹

Barry Greene, chief executive officer of Scholar Rock, emphasized the significance of the FDA submission, stating, "This milestone marks a crucial step forward in our mission to develop transformative therapies for SMA. We remain dedicated to working alongside regulators, clinicians, and the SMA community to bring apitegromab to patients as swiftly as possible".¹

References:

1. Scholar Rock submits biologics license application (BLA) to the US FDA for apitegromab as a treatment for patients with spinal muscular atrophy (SMA). Scholar Rock. Press release. January 29, 2025. Accessed February 3, 2025. https://investors.scholarrock.com/news-releases/news-release-details/scholar-rock-submits-biologics-license-application-bla-us-fda

2. Scholar Rock Reports Apitegromab Meets Primary Endpoint in Phase 3 SAPPHIRE Study in Patients with Spinal Muscular Atrophy (SMA). Scholar Rock. Press release. October 7, 2024. Accessed February 3, 2025. https://investors.scholarrock.com/news-releases/news-release-details/scholar-rock-reports-apitegromab-meets-primary-endpoint-phase-3