Sanofi Faces CRL Setback on MS Drug While Securing EU Win for BTK Inhibitor

Sanofi disclosed a significant regulatory hurdle this week as the FDA issued a complete response letter (CRL) regarding its application for tolebrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor targeting non-relapsing secondary progressive multiple sclerosis (nrSPMS) in adults. The setback represents the second major revision to the approval timeline within months, with the agency now expected to provide further guidance by Q1 2026.

Regulatory Delays Compound Earlier Clinical Disappointments

The CRL decision follows a pattern of mounting challenges for Sanofi’s BTK inhibitor program. Earlier this year, the FDA extended the tolebrutinib review period twice—first by three months in the spring, then again after the company submitted an expanded access protocol at the regulator’s request. The initial decision date of September 28, 2025, was pushed to December 28, then further delayed to early 2026.

The timing aligns with fresh clinical setbacks. In recent weeks, Sanofi revealed that its phase III PERCEUS trial evaluating tolebrutinib in primary progressive MS (PPMS) failed to meet primary endpoints for slowing disability progression. The company subsequently decided to halt further development in PPMS, which represents approximately 10% of the MS patient population. Despite the efficacy concerns, the safety profile remained consistent with prior studies.

These challenges echo 2022, when the FDA imposed a partial clinical hold on tolebrutinib studies after identifying drug-induced liver injury cases in trial participants. While the company eventually discontinued separate myasthenia gravis trials, the MS indication continued moving forward—until now.

Market Performance and Analyst Outlook

SNY shares have gained just 1.1% over the past six months, materially underperforming the broader healthcare sector’s 20.4% rise, reflecting market skepticism about the drug’s path forward. The CRL and recent trial failure suggest a rank-and-file reassessment of Sanofi’s pipeline strength in neurology.

However, the company scored a significant win internationally. The European Commission approved Wayrilz (rilzabrutinib), another BTK inhibitor, for treating adult patients with immune thrombocytopenia (ITP) who have failed other therapies. This approval followed a positive committee opinion in October and was supported by phase III LUNA 3 trial data demonstrating improvements in sustained platelet counts. The FDA had already cleared Wayrilz for chronic ITP in August 2025.

What’s Next for Investors

The divergent fortunes of Sanofi’s pipeline—stalled on MS but advancing in ITP—underscore the unpredictability of drug development. With further CRL guidance expected by March 2026, the company faces critical decisions about tolebrutinib’s commercial viability. Market watchers are tracking whether additional data submissions can revive the application or whether Sanofi will pivot resources toward its validated BTK programs in hematologic indications.