The FDA rejected Sanofi's application for tolebrutinib to treat nonrelapsing secondary progressive multiple sclerosis (nrSPMS) in December 2025, issuing a Complete Response Letter indicating the application will not be approved in its present form12
Tolebrutinib received backing from the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) in April 2026, marking a significant divergence between U.S. and European regulatory decisions6
Tolebrutinib was previously granted FDA Breakthrough Therapy and Priority Review designations for nrSPMS, recognizing its potential to address disability progression as an unmet medical need in MS14
The drug is designed to target smoldering (chronic) neuroinflammation rather than acute MS inflammation, potentially distinguishing it from other disease-modifying MS therapies2
Tolebrutinib was approved in the United Arab Emirates in July 2025, marking its first worldwide approval prior to the EMA decision2
Sanofi's development program faced multiple setbacks including a partial clinical hold due to drug-induced liver injury reports and failure of two of three Phase 3 trials in relapsing MS forms14
The Phase 3 PERSEUS trial testing tolebrutinib in primary progressive MS (PPMS) failed to meet its primary endpoint, leading Sanofi to discontinue pursuit of PPMS approval24
Sources:
1. https://www.fiercebiotech.com/biotech/sanofi-corcept-surprised-fda-rejections-ms-cushings-syndrome-drugs
2. https://multiplesclerosisnewstoday.com/news-posts/2025/12/29/fda-denies-tolebrutinib-approval-nonrelapsing-progressive-ms/
4. https://www.medcentral.com/neurology/ms/fda-extends-review-tolebrutinib-for-non-relapsing-ms
6. https://insights.citeline.com/pink-sheet/product-reviews/eu-chmp/sanofis-tolebrutinib-gets-ema-backing-after-failing-to-win-over-us-regulators-BRGAODLQGVE7HPTOYSUCDBVWBM/