Sanofi's Tolebrutinib Faces FDA Setback With Complete Response Letter On SPMS Treatment

Sanofi (SNY, SAN.PA) has encountered a regulatory hurdle as the U.S. Food and Drug Administration issued a complete response letter regarding its tolebrutinib application for treating non-relapsing secondary progressive multiple sclerosis (nrSPMS) in adult patients. This development represents a significant obstacle in the drug’s path toward U.S. market approval.

The pharmaceutical giant expressed its disappointment with the FDA’s decision, emphasizing that the regulatory body should integrate feedback from medical professionals, scientific researchers, and patient advocacy groups to present a more comprehensive perspective on the medication’s benefits. Sanofi stated its commitment to collaborating with the FDA to identify alternative pathways for tolebrutinib approval and ultimately address the needs of the multiple sclerosis community.

Understanding Tolebrutinib’s Mechanism and Potential

Tolebrutinib functions as an investigational oral brain-penetrant Bruton’s tyrosine kinase inhibitor, engineered specifically to address smoldering neuroinflammation—a primary contributor to progressive disability in multiple sclerosis patients. This targeted approach distinguishes the compound from conventional MS treatments and highlights its therapeutic significance.

The regulatory review timeline has already extended past the original target action date of December 28, 2025. Sanofi had previously indicated on December 15, 2025, that the FDA review would likely exceed this deadline, with the company anticipating additional regulatory guidance by the end of Q1 2026.

Global Progress and Financial Implications

Despite the U.S. setback, tolebrutinib achieved provisional approval in the United Arab Emirates in July 2025 for nrSPMS treatment and to decelerate disability progression independent of relapse activity. The drug remains under active regulatory evaluation across European Union markets and other global jurisdictions.

In response to FDA requests, Sanofi submitted an expanded access protocol for the investigational treatment. Concurrently, the company is conducting an impairment evaluation under IFRS (IAS 36) guidelines to assess the intangible asset value tied to tolebrutinib. Results from this financial assessment will be disclosed alongside Sanofi’s Q4 and full-year 2025 earnings in January 2026.

The company clarified that the impairment test outcome will not influence net business income or earnings per share calculations, with 2025 financial guidance remaining intact. On December 23, 2025, Sanofi’s stock closed at $48.32, gaining $0.29 or 0.60%, showing modest market resilience to the regulatory announcement.

The complete response letter marks a critical juncture for tolebrutinib’s U.S. development strategy, requiring Sanofi to reassess its submission approach while maintaining engagement with FDA stakeholders.