Sanofi Stumbles as FDA Rejects Key Multiple Sclerosis Drug
The complete response letter for tolebrutinib marks a significant blow to the French drugmaker's neurology pipeline and a drug once seen as a potential blockbuster.
Sanofi announced Tuesday that it has received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration for its investigational multiple sclerosis drug, tolebrutinib, a significant setback for the $117 billion pharmaceutical giant and its ambitions in the neurology space.
The French company disclosed that the FDA rejected its application for tolebrutinib for the treatment of non-relapsing secondary progressive multiple sclerosis (nrSPMS), a debilitating form of the disease with limited treatment options. The news is a major blow for a drug that Sanofi had touted as a key future growth driver and which analysts once projected could reach global sales of $1.4 billion by 2031.
The rejection came as a surprise to many, including Sanofi itself. Tolebrutinib had been granted a Breakthrough Therapy designation by the FDA, a status intended to expedite the review of drugs for serious conditions. The company stated it was “significantly disappointed” with the outcome, noting the decision marked a “substantial change” from previous agency feedback, which had led Sanofi to believe a regulatory delay into early 2026 was the most likely hurdle, not an outright rejection.
This CRL is the latest in a series of blows for the once-promising drug candidate. Tolebrutinib, a type of drug known as a Bruton’s tyrosine kinase (BTK) inhibitor, has stumbled in other clinical trials recently. In late 2025, Sanofi announced the drug failed to meet its primary endpoint in a Phase 3 study for primary progressive MS (PPMS), forcing the company to abandon that indication. This followed an earlier failure in trials for relapsing forms of MS.
The successive failures now cast a dark shadow over the entire tolebrutinib program, which was central to Sanofi's strategy to build a leading neurology franchise. The company's inability to bring the drug to market for any form of multiple sclerosis deals a heavy blow to its late-stage pipeline and cedes a significant advantage to competitors.
The competitive landscape for BTK inhibitors in MS is fierce, with rivals like Roche, Novartis, and Merck KGaA developing their own candidates. Roche's fenebrutinib, in particular, has shown promising results, and Sanofi's setback could pave a clearer path to market for its competitors in a therapeutic area with high unmet need.
Even as it faces this significant clinical disappointment, Sanofi is not standing still. In a separate announcement on the same day, the company revealed a deal to acquire Dynavax, a move that adds a marketed hepatitis B vaccine and a clinical-stage shingles candidate to its portfolio. The acquisition signals an effort to bolster its pipeline in other areas, particularly vaccines, potentially to offset the weakness exposed in its internal neurology R&D program.
Investors will now be closely watching Sanofi's next steps. The company has stated it is evaluating the FDA’s feedback to determine the path forward for tolebrutinib. However, with multiple late-stage failures and a surprise rejection for its most promising indication, the future for the drug looks uncertain, placing greater pressure on other assets in Sanofi's pipeline to perform.