Sanofi Shares Hit by Double Setback for MS Drug Tolebrutinib
The French drugmaker's pivotal Phase 3 trial for one form of multiple sclerosis failed, while US regulators delayed a decision on another, jeopardizing a key pipeline asset.
Sanofi’s ambitions in the competitive multiple sclerosis market suffered a significant blow on Monday following a dual setback for its high-stakes oral medication, tolebrutinib. The Paris-based pharmaceutical giant announced that a pivotal Phase 3 trial for the drug in primary progressive multiple sclerosis (PPMS) failed to meet its primary goal, and separately, that a U.S. regulatory decision for another form of the disease would be delayed.
The news casts a pall over a drug central to Sanofi’s pipeline strategy, which was acquired through the $3.7 billion purchase of Principia Biopharma in 2020. The company’s American depositary receipts (SNY) started the day at $48.68, with the latest developments posing a considerable headwind against an average analyst price target of over $60.
The more definitive setback came from the PERSEUS study, which evaluated tolebrutinib in patients with PPMS, a debilitating form of the disease with limited treatment options. According to the company's press release, the trial did not demonstrate a statistically significant delay in disability progression compared to a placebo. As a result, Sanofi confirmed it would not pursue regulatory approval for the drug in this specific indication.
This failure solidifies the market dominance of Roche's Ocrevus, the primary approved treatment for PPMS. Breaking into this challenging therapeutic area was a key goal for tolebrutinib, which as a Bruton's tyrosine kinase (BTK) inhibitor, was hoped to offer a new mechanism of action for patients.
Compounding the trial failure, Sanofi delivered concurrent disappointing news on the regulatory front for a different indication. The company disclosed that the U.S. Food and Drug Administration (FDA) review for tolebrutinib in treating non-relapsing secondary progressive multiple sclerosis (nrSPMS) will extend beyond the expected December 28, 2025, target action date. Sanofi now anticipates further guidance from the agency by the end of the first quarter of 2026.
The delay was prompted by the FDA classifying additional data submitted by Sanofi as a "major amendment," which requires more time for a full review. This extension adds to investor uncertainty, particularly around the drug's safety profile. Tolebrutinib has been associated with a risk of drug-induced liver injury (DILI), a factor that has drawn regulatory scrutiny and which analysts believe is central to the extended review. Prior to the delay, some analysts had estimated a 65-70% probability of approval for the nrSPMS indication, a figure that may now be revised downwards.
The dual announcements throw the future of the entire tolebrutinib program, once projected to achieve blockbuster sales, into question. In its statement, Sanofi noted it will conduct an impairment test on the intangible asset value of the drug, with the results to be disclosed with its fourth-quarter 2025 financial results. Such a move signals the company is formally assessing a potential write-down on its multibillion-dollar investment.
Houman Ashrafian, Sanofi's Head of Research and Development, maintained the company's commitment to the MS community and expressed continued confidence in tolebrutinib's potential for patients with relapsing forms of the disease. However, with the PPMS pathway now closed and the nrSPMS decision clouded by delay and safety questions, investors will be keenly awaiting the full data presentation at an upcoming medical conference and the FDA's final verdict in 2026 to determine what value, if any, is left in the costly program.