US Regulatory Review Update: Tolebrutinib for Non-Relapsing Secondary Progressive MS

The U.S. Food and Drug Administration (FDA) has extended the target action date for its review of Sanofi’s new drug application (NDA) for tolebrutinib by three months, now set for December 28, 2025. Tolebrutinib is an oral, brain-penetrant Bruton’s tyrosine kinase (BTK) inhibitor being developed to treat non-relapsing, secondary progressive multiple sclerosis (nrSPMS) and to slow disability progression independent of relapse activity in adult patients.

The extension follows the submission of additional analyses during the review, which the FDA classified as a major amendment to the NDA. Sanofi remains optimistic about tolebrutinib’s potential benefits and is working closely with the FDA throughout the review process.

Tolebrutinib was the first brain-penetrant BTK inhibitor in nrSPMS to receive breakthrough therapy designation from the FDA. The regulatory evaluation is based on pivotal data from the global, double-blind, randomized phase 3 HERCULES and GEMINI 1 and 2 studies, which assessed the efficacy and safety of tolebrutinib in patients with nrSPMS and relapsing multiple sclerosis (RMS), respectively.

While the FDA has yet to establish the safety and efficacy of tolebrutinib, the drug is also under regulatory review worldwide, including in the European Union. Meanwhile, the PERSEUS phase 3 trial in primary progressive multiple sclerosis is ongoing, with results expected in the second half of 2025.