Scholar Rock Submits FDA Application for Apitegromab to Improve Motor Function in Spinal Muscular Atrophy

Scholar Rock submitted a biologics license application (BLA) to the FDA for apitegromab as a muscle-targeted therapy for improvement of motor function in individuals with spinal muscular atrophy (SMA) who are receiving survival motor neuron (SMN)-target treatments. The company will also file a marketing authorization application with the European Medicines Agency in the first quarter of 2025.¹

The FDA previously granted fast track, orphan drug, and rare pediatric disease designations for apitegromab. | Image Credit: Rochu_2008 | stock.adobe.com

“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, as measured by the Hammersmith Functional Motor Scale-Expanded at week 52,” Jing Marantz, MD, PhD, chief medical officer of Scholar Rock, said in a news release. “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.”¹

The submission is based on data from the phase 3 SAPPHIRE (NCT05156320) trial and the phase 2 TOPAZ (NCT03921528) trial. In the SAPPHIRE trial, investigators included patients 2 years of age or older at screening who were previously diagnosed with later-onset SMA. Patients also received approved SMN upregulator therapy (nusinersen [Spinraza; Biogen] or risdiplam [Evrysdi; Genentech]). Investigators aimed to confirm the efficacy and safety of apitegromab as an adjunct therapy to either SMN.^1,2

The study met its primary end point of a statistically significant and clinically meaningful improvement for apitegromab compared with the placebo in motor function. The investigators found that the mean difference in change from baseline Hammersmith Functional Motor Scale Expanded (HFMSE) was 1.8 points (p = 0.0192) in individuals aged 2 years to 12 years taking 10 mg/kg and 20 mg/kg of apitegromab compared with the placebo. Further, patients receiving 20 mg/kg of apitegromab had a 1.4-point mean difference when compared with the placebo (p = 0.1149).³

Approximately 30% of patients receiving apitegromab had a 3-point or greater improvement in HFMSE compared with 12.5% of those receiving the placebo. Early motor function improvement was first measured at 8 weeks for patients receiving apitegromab, with the benefits increasing at week 52. Treatment was well-tolerated across all age groups, with no clinically relevant differences in the safety profile by dose. There were no new safety signals identified in the clinical trial compared with the TOPAZ clinical trial. Furthermore, there were no drug discontinuations due to adverse events.³

The FDA previously granted fast track, orphan drug, and rare pediatric disease designations for apitegromab. Scholar Rock also requested priority review for the drug, which would shorten the review time to 6 months from the date of filing acceptance if granted. The company will also be conducting a study for patients with SMA under 2 years of age.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). News release. Scholar Rock. January 29, 2025. Accessed January 30, 2025. https://www.businesswire.com/news/home/20250129052122/en/Scholar-Rock-Submits-Biologics-License-Application-BLA-to-the-U.S.-FDA-for-Apitegromab-as-a-Treatment-for-Patients-with-Spinal-Muscular-Atrophy-SMA

2. Efficacy and Safety of Apitegromab in Patients With Later-Onset Spinal Muscular Atrophy Treated With Nusinersen or Risdiplam (SAPPHIRE). ClinicalTrials.gov identification: NCT05156320. Updated May 13, 2024. Accessed January 30, 2025. https://clinicaltrials.gov/study/NCT05156320

3. Scholar Rock reports apitegromab meets primary endpoint in phase 3 SAPPHIRE study in patients with spinal muscular atrophy (SMA). News release. October 7, 2024. Accessed January 30, 2025. https://investors.scholarrock.com/news-releases/news-release-details/scholar-rock-reports-apitegromab-meets-primary-endpoint-phase-3