EU panel backs Sanofi’s tolebrutinib for secondary progressive multiple sclerosis
The EMA’s CHMP recommended approval of Sanofi’s Cenrifki (tolebrutinib) for non-relapsing secondary progressive multiple sclerosis. The phase 3 HERCULES study showed reduced disability progression, while liver injury remains an identified safety risk.
The European Medicines Agency’s Committee for Medicinal Products for Human Use adopted a positive opinion recommending approval of Cenrifki (tolebrutinib) for treating secondary progressive multiple sclerosis without relapses in the last two years. The recommendation was based on data from the HERCULES phase 3 study in non-relapsing SPMS, with supporting data from the GEMINI 1 and GEMINI 2 phase 3 studies in relapsing multiple sclerosis.
The CHMP cited the benefits of tolebrutinib, including a 31% reduction in disability progression and a 38% reduction in new or enlarging lesions per year compared with patients on placebo. The studies demonstrated that the brain-penetrant drug significantly delayed the onset of disability progression in non-relapsing SPMS.
A final decision from the European Medicines Agency is expected in the coming months. Additional submissions for Cenrifki are currently under review with regulatory authorities worldwide.
The most common adverse events reported were COVID-19 and upper respiratory tract infections. Significant liver enzyme elevations were also observed. Drug-induced liver injury is an identified safety risk of tolebrutinib, requiring strict adherence to liver monitoring requirements and prompt management of liver enzyme elevations.
Last year, Sanofi announced two regulatory delays in the United States before the FDA rejected the treatment in the same indication in December, citing efficacy and safety issues. In its complete response letter, the agency said that “a favorable benefit-risk profile could not be established for any patient subpopulation,” for tolebrutinib.
Sanofi had previously said it anticipated that the review process for the ongoing U.S. regulatory review of tolebrutinib in non-relapsing secondary progressive multiple sclerosis would extend beyond the previously communicated target action date of December 28, 2025, and expected further guidance from the FDA by the end of the first quarter of 2026. In response to an FDA request, Sanofi submitted an expanded access protocol for tolebrutinib in nrSPMS.
Tolebrutinib is an investigational, oral, brain-penetrant Bruton’s tyrosine kinase inhibitor designed to target neuroinflammation in multiple sclerosis. Secondary progressive multiple sclerosis typically refers to people with a previous diagnosis of relapsing MS who have stopped experiencing relapses but continue to experience disability accumulation, in the absence of relapses.