High Dose Nusinersen, Apitegromab Receive CRLs, Tolebrutinib PDUFA Pushed Back

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Welcome to this special edition of Neurology News Network. I'm Marco Meglio.

The FDA has handed Biogen a complete response letter (CRL) over its submission for a higher, potentially more effective, dose of nusinersen (Spinraza), an approved therapy for children with spinal muscular atrophy (SMA). In the letter, the FDA requested an update to the technical information be included in the Chemistry Manufacturing and Controls module of the supplemental new drug application (sNDA) but did not cite any deficiencies in the clinical data presented in the package. The agency gave some potential resolutions for the submission, and Biogen is planning to resubmit the application as soon as information becomes ready.

Following observations from a routine inspection at Novo Nordisk’s facility, the FDA has issued Scholar Rock a complete response letter (CRL) for the biologics license application (BLA) of apitegromab, an investigational monoclonal antibody for the treatment of spinal muscular atrophy (SMA). Scholar noted that these inspection findings were not specific to the agent and that the CRL did not cite concerns regarding its efficacy, safety, or the third-party drug substance manufacturer. According to Scholar Rock’s second-quarter 2025 earnings announcement, Novo Nordisk submitted a comprehensive response to the FDA in early August 2025 and continued implementing corrective actions while providing the agency with progress updates. Scholar Rock reported that it plans to resubmit the BLA for apitegromab after the FDA confirms remediation of the manufacturing findings, anticipating that the agency will review the application once those issues are resolved.

Tolebrutinib, an investigational, oral, brain-penetrant Bruton tyrosine kinase (BTK) inhibitor under review for the treatment of nonrelapsing secondary progressive multiple sclerosis (nrSPMS), will have its review period pushed back to later this year, according to Sanofi, the drug manufacturer. The FDA noted that additional information constituted a major amendment to the new drug application, leading to a new Prescription Drug User Fee Act decision date of December 28, 2025. Sanofi’s application for tolebrutinib included data from the global phase 3 HERCULES study (NCT04411641) in nrSPMS, as well as the phase 3 GEMINI 1 and 2 trials (NCT04410978; NCT04410991) of patients with relapsing MS. If approved, tolebrutinib will become the only marketed BTK available for the treatment of MS as well as the first marketed BTK specific to patients with nrSPMS.

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