Unexpected setback from the U.S. regulator In a surprising turn of events, Sanofi received a Complete Response Letter (CRL) from the FDA, declining the approval of its oral BTK inhibitor, tolebrutinib, for non-relapsing secondary progressive multiple sclerosis (nrSPMS). The timing caught the French drugmaker off guard, as the verdict arrived months ahead of the expected review timeline in early 2026.
Just weeks prior, Sanofi had been working on an expanded access protocol at the regulator’s request, believing the decision deadline had been extended.
Controversy over clinical milestones and unmet needs Houman Ashrafian, Sanofi’s head of R&D, expressed significant disappointment, noting that the CRL represents a “meaningful change in direction” from previous FDA feedback. The drug’s journey has been a mix of highs and lows:
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Positive signals: The HERCULES trial showed tolebrutinib could delay six-month disability progression by 31% compared to a placebo.
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Previous failures: The drug previously failed two Phase 3 trials in relapsing forms of MS and a pivotal trial in primary progressive MS (PPMS).
Competitive landscape and global outlook This rejection hands a strategic advantage to Roche, whose rival BTK inhibitor, fenebrutinib, recently met primary endpoints in Phase 3 trials and is preparing for regulatory filings next year. While the U.S. market remains closed for now, tolebrutinib has already secured its first approval in the United Arab Emirates (UAE) and continues to await decisions from other global regulators, including the European Medicines Agency (EMA).
Source: https://pharmaphorum.com/news/no-christmas-present-sanofi-fda-turns-down-ms-drug