FDA Extends Review Period for Novel MS Drug Tolebrutinib

The Food and Drug Administration (FDA) has extended the review period of the New Drug Application (NDA) for tolebrutinib for the treatment of non-relapsing, secondary progressive multiple sclerosis (nrSPMS) and to slow disability accumulation independent of relapse activity in adult patients.

The Agency had originally set a Prescription Drug User Fee Act (PDUFA) date of September 28, 2025 for completion of the review; however, the submission of additional analyses by Sanofi was deemed to be a major amendment to the application requiring a 3 month extension. The new PDUFA target date is now December 28, 2025.

Tolebrutinib is an investigational oral brain-penetrant Bruton tyrosine kinase inhibitor. The NDA submission is supported by data from the phase 3 HERCULES (ClinicalTrials.gov Identifier: NCT04411641), GEMINI 1 (ClinicalTrials.gov Identifier: NCT04410978) and GEMINI 2 (ClinicalTrials.gov Identifier: NCT04410991) trials. In HERCULES, treatment with tolebrutinib delayed the time to onset of 6-month confirmed disease progression by 31% compared with placebo (P =.0026) in patients with nrSPMS. 

The GEMINI 1 and GEMINI 2 trials compared treatment with tolebrutinib with teriflunomide in patients with relapsing MS. Neither trial met the primary endpoint of statistically significant improvement in annualized relapse rates; however in a pooled analysis, tolebrutinib delayed the time to onset of 6-month confirmed disability worsening by 29% (P =.023).

Tolebrutinib is also being investigated in the phase 3 PERSEUS trial (ClinicalTrials.gov Identifier: NCT04458051) in patients with primary progressive MS. Study results are expected in the second half of 2025. 

This article originally appeared on MPR