Sanofi’s multiple sclerosis drug tolebrutinib flunks Phase 3 in PPMS and faces another FDA PDUFA delay

Sanofi’s Bruton’s tyrosine kinase (BTK) inhibitor tolebrutinib failed its Phase 3 PERSEUS trial in primary progressive multiple sclerosis (PPMS), missing the primary endpoint of delaying 6‑month composite confirmed disability progression.1 2 3

Based on the negative PERSEUS results, Sanofi will not pursue regulatory registration of tolebrutinib for PPMS.1 2 3 4

The PERSEUS study enrolled 767 PPMS patients and was designed to assess whether tolebrutinib could better delay disability progression versus control.1 4

Separate from the trial failure, the planned U.S. PDUFA decision for tolebrutinib in non‑relapsing secondary progressive MS (nrSPMS) has been delayed again, marking a second consecutive FDA action date extension.1 3 5

Sanofi now expects new guidance from the FDA by the end of March regarding the rescheduled PDUFA timeline for the nrSPMS indication.3 5

Sanofi has confirmed it is continuing to pursue approval in nrSPMS, where tolebrutinib previously showed a positive late‑stage result, despite failures in other MS populations.1 3 5

Tolebrutinib has had a troubled development history, including a prior partial clinical hold by the FDA in 2022 over liver injury concerns and failures in two of three late‑stage MS studies, leading Sanofi to drop development for relapsing MS earlier in 2025.1 3

Sanofi acquired tolebrutinib through its $3.7 billion acquisition of Principia Biopharma in 2021, and is now evaluating a potential impairment charge related to the asset’s intangible value; any charge is not expected to affect 2025 net income or EPS guidance.1

Tolebrutinib received a provisional approval in the United Arab Emirates in July 2025 for treatment of non‑relapsing secondary progressive MS, highlighting regulatory divergence across regions.2

Sanofi executives framed the failed PPMS outcome as disappointing but potentially informative for understanding MS biology, while reiterating that overall 2025 financial guidance remains unchanged despite the setback.1 2

Sources:

1. https://www.biopharmadive.com/news/sanofi-primary-progressive-ms-tolebrutinib-fda-delay/807865/

2. https://www.sanofi.com/en/media-room/press-releases/2025/2025-12-15-06-05-00-3205094

3. https://www.fiercebiotech.com/biotech/sanofis-tolebrutinib-woes-pile-fda-delay-trial-miss

4. https://pharmaphorum.com/news/sanofi-gets-double-blow-ms-drug-tolebrutinib

5. https://www.news.sanofi.us/2025-12-15-Sanofi-provides-update-on-tolebrutinib-regulatory-submission-in-non-relapsing-secondary-progressive-multiple-sclerosis

Sources:

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