Sanofi's Multiple Sclerosis Drug Faces Fresh FDA Hurdle as CRL Delays Approval Timeline

Sanofi’s BTK inhibitor tolebrutinib hit another regulatory roadblock when the FDA issued a complete response letter (CRL) rejecting the drug’s application for treating non-relapsing secondary progressive multiple sclerosis (nrSPMS) in adults. The setback marks the second major delay this year, as the agency had already extended its review deadline twice—first by three months to December 2025, then again to the end of Q1 2026 after the company submitted an expanded access protocol.

The Regulatory Roller Coaster: Timeline of Delays

The tolebrutinib approval journey has been anything but smooth. The FDA initially set a decision date of September 28, 2025, but classified Sanofi’s additional clinical analyses as a major amendment, pushing the deadline to December. When the company submitted an expanded access program at the FDA’s request, the agency revised expectations once more, with further guidance now expected by March 2026. This pattern of extensions often signals underlying concerns about efficacy or safety data during the review process.

Meanwhile, SNY shares have gained just 1.1% over the past six months, significantly lagging the broader healthcare sector’s 20.4% increase during the same period—a performance gap that reflects investor concerns about the pipeline.

Clinical Setbacks Compound Regulatory Pressures

Beyond the nrSPMS hurdle, Sanofi announced disappointing trial results for tolebrutinib in primary progressive MS (PPMS). The phase III PERCEUS study failed to demonstrate efficacy in slowing disability progression compared to placebo, prompting the company to abandon development in this indication despite PPMS affecting roughly 10% of the MS patient population.

The drug’s troubled past also weighed on development timelines. In 2022, the FDA imposed a partial clinical hold on tolebrutinib studies across multiple indications after identifying drug-induced liver injury in trial participants. While MS programs continued under modified protocols, the myasthenia gravis studies were discontinued entirely as the competitive landscape shifted.

A Silver Lining: Wayrilz Wins EU Approval

Not all of Sanofi’s BTK inhibitor portfolio faces headwinds. The European Commission approved Wayrilz (rilzabrutinib) for immune thrombocytopenia (ITP) in treatment-resistant patients, following a positive opinion from the European Medicines Agency. The approval was backed by phase III LUNA 3 data showing sustained platelet count improvements and symptom relief. The FDA had already greenlit Wayrilz for persistent or chronic ITP in August 2025, giving Sanofi at least one regulatory win to offset the tolebrutinib delays.

What’s Next for the CRL and Investor Sentiment

The complete response letter on tolebrutinib effectively resets the approval timeline, requiring Sanofi to address FDA concerns before resubmission. Given the mounting clinical challenges and regulatory scrutiny, commercialization remains uncertain. For traders monitoring SNY, the stock’s underperformance relative to sector peers suggests that confidence in the pipeline recovery remains shaky until clearer regulatory signals emerge.