Sanofi announced that its multiple sclerosis drug, tolebrutinib, did not achieve its main goal in a Phase III clinical trial for primary progressive multiple sclerosis (PPMS). The company also said the U.S. Food and Drug Administration (FDA) has again delayed its decision on the drug’s approval application for another form of the disease.
The Phase III PERSEUS trial tested tolebrutinib, a BTK inhibitor, in patients with PPMS, which accounts for about 10% of all MS cases. The study failed to show a benefit in slowing disability progression compared to placebo. Sanofi did not release detailed data from the trial but stated it would no longer seek regulatory approval for tolebrutinib in PPMS.
Leerink Partners had previously predicted positive results from this study and expected that Sanofi’s drug could outperform Roche’s approved treatment Ocrevus in delaying disease progression at week 24. However, these expectations were not met.
Sanofi’s press release did not include detailed safety information regarding potential liver injury associated with tolebrutinib. The company only noted that safety outcomes were consistent with earlier studies. Leerink Partners had been waiting for this information to assess the likelihood of FDA approval for tolebrutinib in secondary progressive multiple sclerosis (SPMS).
On the regulatory side, the FDA has once more postponed its decision on whether to approve tolebrutinib for non-relapsing secondary progressive multiple sclerosis (nrSPMS). In September, the agency moved its timeline back to December 28, but Sanofi now says there is no new firm date. The FDA requested more details about an expanded access protocol for nrSPMS and will provide an updated decision date by the end of the first quarter of 2026.
Leerink described these developments as “disappointing” and had projected annual sales of approximately $1.1 billion for the drug.
Other companies are also developing similar treatments. Roche is working on fenebrutinib, another BTK inhibitor that has shown comparable efficacy to Ocrevus in PPMS.
Tolebrutinib has faced several challenges during development, including prior clinical failures and reports of liver injury that led to FDA-imposed holds on trials. In September 2024, Sanofi reported positive results from the HERCULES trial showing a 31% reduction in disease progression among nrSPMS patients. These findings supported Sanofi’s regulatory filing now facing further delay.
The HERCULES study also found increased adverse events such as elevated liver enzymes in 4.1% of patients treated with tolebrutinib; most cases resolved without major issues, but one patient died after a liver transplant due to post-operative complications. As a result, Sanofi made changes to increase liver monitoring during studies.
Tolebrutinib is an oral small molecule that inhibits BTK protein activity involved in B cell function and microglia-driven disease processes.
Sanofi acquired rights to develop and market tolebrutinib through its $3.7 billion purchase of Principia Biopharma in August 2020.
