Sanofi Provides Updates on Tolebrutinib for PPMS and NrSPMS

Treatment with the investigational Bruton tyrosine kinase (BTK) inhibitor tolebrutinib (Sanofi, Bridgewater, NJ) did not delay disability progression in people with primary progressive multiple sclerosis (PPMS), according to new results reported from the phase 3 PERSEUS clinical trial (NCT04458051). The study did not meet its primary efficacy endpoint of demonstrating that tolebrutinib delayed time to 6-month composite confirmed disability progression (cCDP) compared with placebo. Based on these findings, Sanofi stated it will not pursue regulatory registration of tolebrutinib for PPMS. In another announcement, Sanofi provided an update on the regulatory submission for tolebrutinib treatment for nonrelapsing secondary progressive multiple sclerosis (nrSPMS), stating that the review process is expected to extend beyond the US target action date of December 28, 2025.

PERSEUS was a global, randomized, double-blind, placebo-controlled phase 3 trial evaluating the efficacy and safety of oral tolebrutinib in adults with PPMS. Participants were randomized 2:1 to receive treatment with tolebrutinib or placebo daily for an approximate duration of ≤60 months. Eligible participants were aged 18 to 55 years, met the 2017 revised McDonald criteria for PPMS, had an Expanded Disability Status Scale (EDSS) score between 2.0 and 6.5 at screening, and had positive cerebrospinal fluid findings. Participants also had no access to, intolerance of, or perceived lack of efficacy with Ocrevus (ocrelizumab; Genentech, South San Francisco, CA). The primary end point was time to 6-month cCDP, defined by sustained worsening on EDSS, the Timed 25-Foot Walk, or the 9-Hole Peg Test. Secondary endpoints included MRI outcomes, cognitive measures, quality of life, and safety.

Key points from the statement released by Sanofi include the following:

• Sanofi will not seek regulatory approval of tolebrutinib for the treatment of PPMS based on the new results.
• The safety profile of tolebrutinib in PERSEUS was consistent with previous studies, with drug-induced liver injury identified as a known risk.
• Strict liver monitoring and prompt management of liver enzyme elevations were emphasized to mitigate the risk of liver injury.
• Full efficacy and safety data from PERSEUS will be presented at a future medical meeting.

Source: Sanofi. Press release: Sanofi provides update on tolebrutinib in primary progressive multiple sclerosis. Sanofi. Published 15 December, 2025. Accessed 19 December, 2025. https://www.sanofi.com/en/media-room/press-releases/2025/2025-12-15-06-05-00-3205094

Sanofi. Press release: Sanofi provides update on tolebrutinib regulatory submission in non-relapsing secondary progressive multiple sclerosis. Sanofi. Published 15 December, 2025. Accessed 22 December, 2025. https://www.sanofi.com/en/media-room/press-releases/2025/2025-12-15-06-00-00-3205091