Sanofi's MS Drug Tolebrutinib Faces Setbacks in Clinical Trials and Regulatory Review

Sanofi, the French pharmaceutical giant, has encountered significant challenges with its multiple sclerosis (MS) drug candidate tolebrutinib. Recent developments have cast a shadow over the drug's future, impacting both its clinical trial outcomes and regulatory approval process.

Failed Phase III Trial in Primary Progressive MS

Tolebrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, has failed to meet its primary endpoint in the Phase III PERSEUS trial for primary progressive multiple sclerosis (PPMS). The study, which enrolled 767 participants, aimed to evaluate the drug's ability to delay disability progression compared to placebo. Sanofi has not released specific data but confirmed that it will not pursue regulatory applications for tolebrutinib in PPMS based on these results.

This setback is particularly significant as PPMS affects approximately 10% of MS patients and represents an area of high unmet medical need. The failure in PPMS narrows the potential therapeutic scope for tolebrutinib, which Sanofi acquired through its $3.7 billion purchase of Principia Biopharma in 2020.

Regulatory Delays for Secondary Progressive MS Application

Compounding the clinical trial disappointment, Sanofi is facing delays in the regulatory review process for tolebrutinib in non-relapsing secondary progressive multiple sclerosis (nrSPMS). The U.S. Food and Drug Administration (FDA) has indicated that it will not meet the previously set decision date of December 28, 2025. This marks the second consecutive delay for the application, following an earlier postponement from September 2025.

Sanofi now anticipates receiving updated guidance from the FDA by the end of the first quarter of 2026. The company has submitted an expanded access protocol at the FDA's request, allowing eligible nrSPMS patients to access the drug. Despite the setbacks, Sanofi maintains its belief in tolebrutinib's risk-benefit profile for this indication.

Implications for Sanofi and the MS Treatment Landscape

These developments pose significant challenges for Sanofi's MS program and may impact the company's financial outlook. While Sanofi states that its 2025 financial guidance remains unchanged, it is evaluating the need for an impairment charge related to tolebrutinib's intangible value.

The setbacks for tolebrutinib come amid a competitive landscape in MS treatment, particularly in the BTK inhibitor class. Rival companies, including Roche, have reported more positive outcomes with their BTK inhibitors in MS trials. Roche's fenebrutinib, for instance, recently succeeded in two large MS trials, including one in primary progressive MS.

As Sanofi navigates these challenges, the MS treatment community awaits further developments and potential alternatives for patients with progressive forms of the disease, where treatment options remain limited despite recent advances in MS care.