FDA issues CRL for apitegromab for SMA, citing facility inspection | Image Credit: Contemporary Pediatrics

The FDA has issued a Complete Response Letter (CRL) for Scholar Rock’s biologics license application (BLA) for apitegromab in spinal muscular atrophy (SMA), citing observations at a third-party manufacturing facility, Catalent Indiana LLC.¹

According to a September 23, 2025, press release from the company, the federal agency raised no concerns about apitegromab’s efficacy or safety data. Scholar Rock said it is “continuing to work closely with Catalent Indiana on the FDA’s manufacturing observations so that we can resubmit the apitegromab BLA as soon as possible," according to a statement from David L. Hallal, chairman and CEO of Scholar Rock.

Apitegromab background and data

Apitegromab is an investigational monoclonal antibody that selectively inhibits myostatin activation in skeletal muscle. It is the first muscle-targeted therapy in SMA to show positive phase 3 results. The pivotal SAPPHIRE trial supported the BLA submission, demonstrating that apitegromab provided statistically significant motor function improvements in patients already receiving survival motor neuron (SMN)-targeted treatments.²

The trial enrolled 156 patients aged 2 to 12 years as the main efficacy population. Patients receiving apitegromab achieved a mean 1.8-point improvement on the Hammersmith Functional Motor Scale–Expanded (HFMSE) compared with placebo at 52 weeks, meeting the primary endpoint (2). In subgroup analysis, patients receiving apitegromab 10 mg/kg had a mean improvement of 2.2 points compared with placebo (P = 0.0121). Those receiving 20 mg/kg showed a mean difference of 1.4 points, which was not statistically significant (P = 0.1149).

Overall, 30.4% of patients treated with apitegromab achieved an improvement of more than 3 points in HFMSE, compared with 12.5% of patients in the placebo group (2). Secondary endpoints, including upper limb function and additional mobility measures, also showed favorable trends for apitegromab.

Apitegromab was well tolerated in the trial, with no significant differences in adverse events between dose groups and placebo. The most common events included headache, upper respiratory tract infection, and pyrexia. No drug-related serious adverse events or treatment discontinuations were reported.

Next Steps and Global Outlook

The CRL was issued following a routine FDA inspection of the Catalent Indiana fill-finish facility, which has since submitted a comprehensive response and corrective action plan (1). Scholar Rock said it believes the FDA will be able to act expeditiously on the resubmitted application once the facility issues are resolved.¹

Patient advocacy groups stressed the need to bring a muscle-targeted therapy to the SMA community. Kenneth Hobby, president of Cure SMA, stated that while the delay is disappointing, “we remain enthusiastic about the transformative potential of apitegromab. Muscle strength and motor function are significant unmet needs for many in the SMA community and are fundamental to independence. A gain in motor function can allow someone to participate in important activities of daily living from self-care to work and social interactions, and as such, we urgently await the availability of the first-ever treatment with the potential to address the muscular component of SMA.”

A marketing authorization application for apitegromab is also under review by the European Medicines Agency, with a decision anticipated by mid-2026. Scholar Rock projects a European launch in the second half of 2026, beginning in Germany.

References:

1. FDA issues complete response letter (CRL) for apitegromab as a treatment for patients with spinal muscular atrophy (SMA) solely related to observations identified at Catalent Indiana LLC fillase.-fini sh facility. Press release. Scholar Rock. September 23, 2025. Accessed September 23, 2025. https://www.businesswire.com/news/home/20250923756342/en/FDA-Issues-Complete-Response-Letter-CRL-for-Apitegromab-as-a-Treatment-for-Patients-with-Spinal-Muscular-Atrophy-SMA-Solely-Related-to-Observations-Identified-at-Catalent-Indiana-LLC-Fill-Finish-Facility
2. Fitch J. Apitegromab BLA submitted to FDA for spinal muscular atrophy. Contemporary Pediatrics. Published February 3, 2025. Accessed September 23, 2025. https://www.contemporarypediatrics.com/view/apitegromab-bla-submitted-to-fda-for-spinal-muscular-atrophy