CHMP Backs Tolebrutinib for Non-Relapsing SPMS — With Liver Monitoring Strings Attached

Sanofi's Cenrifki (tolebrutinib) has cleared a critical regulatory hurdle in Europe, but the CHMP's positive opinion comes with explicit hepatic safety obligations that will define how QA and pharmacovigilance teams operationalise its post-approval lifecycle. For regulatory affairs leads preparing EU market entry strategies for BTK inhibitors, the liver monitoring requirements attached to this recommendation are not a footnote -- they are a structural compliance requirement.

The Committee for Medicinal Products for Human Use adopted a positive opinion on 24 April 2026, recommending approval of Cenrifki for the treatment of secondary progressive multiple sclerosis (SPMS) without relapses in the last two years. A final European Commission decision is expected within months. The recommendation is grounded in data from the HERCULES phase 3 study (NCT04411641) in non-relapsing SPMS, with supporting evidence from the GEMINI 1 (NCT04410978) and GEMINI 2 (NCT04410991) phase 3 trials in relapsing MS -- findings presented at ECTRIMS 2024 and AAN 2025, and published in The New England Journal of Medicine.

Tolebrutinib is an oral, brain-penetrant Bruton's tyrosine kinase (BTK) inhibitor designed to target smoldering neuroinflammation, the mechanism implicated in disability accumulation in progressive MS. The safety profile observed across the clinical programme identified drug-induced liver injury (DILI) as a recognised risk, with significant liver enzyme elevations reported. The most common adverse events were COVID-19 and upper respiratory tract infections. Sanofi has stated that strict adherence to liver monitoring requirements and prompt management of enzyme elevations are essential to mitigate DILI risk -- language that signals a robust Risk Management Plan will accompany any marketing authorisation.

For QA directors and regulatory affairs leads, this recommendation signals the need to build hepatic surveillance protocols into pharmacovigilance systems before launch, not after. Additional regulatory submissions for Cenrifki are currently under review with authorities worldwide, meaning teams in multiple jurisdictions should anticipate comparable safety monitoring frameworks as a condition of approval.