Sanofi wins EU approval for tolebrutinib in progressive MS
Sanofi has secured European Commission approval for Cenrifki (tolebrutinib) in adults with secondary progressive multiple sclerosis who have not experienced relapses in the past two years. The approval, which follows a positive opinion from the EMA's Committee for Medicinal Products for Human Use, positions Cenrifki as the first medicine approved in the EU specifically to address disability progression in non-relapsing SPMS (nrSPMS).
Tolebrutinib is an oral, brain-penetrant Bruton's tyrosine kinase (BTK) inhibitor. Its proposed mechanism centres on suppressing smouldering neuroinflammation, a chronic, low-grade inflammatory process within the central nervous system thought to drive the relentless accumulation of disability characteristic of progressive MS. Unlike the relapsing forms of the disease, nrSPMS has historically been resistant to existing disease-modifying therapies, most of which were designed to reduce acute inflammatory episodes rather than the underlying progressive biology.
HERCULES and supporting trial data
The regulatory submission was anchored by the HERCULES phase 3 study (NCT04411641), a double-blind, randomised trial in nrSPMS patients with an expanded disability status scale score between 3.0 and 6.5 and documented disability accumulation in the preceding twelve months. Participants received either oral daily tolebrutinib or placebo for up to approximately 48 months. The primary endpoint was six-month confirmed disability progression. Sanofi reported that HERCULES demonstrated a statistically significant delay in the onset of disability progression, though full magnitude-of-effect figures were not included in the release. Supporting data came from the GEMINI 1 and GEMINI 2 phase 3 studies in relapsing MS, which compared tolebrutinib against teriflunomide on annualised relapse rate.
On safety, the most common adverse events across the clinical programme were COVID-19 and upper respiratory tract infections. Significant liver enzyme elevations were also observed, and drug-induced liver injury (DILI) is identified as a specific safety risk. Sanofi says strict liver monitoring and prompt management of elevations are required to mitigate that risk, and the approval is accompanied by a Risk Management Programme.
Market context and competitive landscape
SPMS without relapses represents one of the most difficult-to-treat segments of the MS market. Approved therapies for progressive forms of the disease have been limited; siponimod (Novartis) carries an EMA label for active SPMS, and ocrelizumab (Roche) is approved for primary progressive MS, but neither is indicated for the non-relapsing SPMS population that tolebrutinib now addresses. The BTK inhibitor class has attracted considerable attention in neuroimmunology, with several other companies including Merck KGaA and Roche running competing programmes, though Cenrifki is the first in the class to reach approval in this specific indication.
Sanofi has said it will launch Cenrifki commercially in Germany in 2026, with other European markets expected to follow through standard national pricing and reimbursement processes. The drug also holds approval in Australia and the UAE. The SPMS disability burden is significant: the release notes that annual MS-related disability costs across major European economies exceed the average annual income per person, and up to 82% of those with severe MS rely on informal caregiving.
The approval strengthens Sanofi's neurology franchise as the company continues to build out a pipeline spanning chronic inflammatory demyelinating polyneuropathy, Alzheimer's disease and Parkinson's disease. For patients with nrSPMS, who have had few meaningful treatment options, the arrival of an EU-approved disability-targeting therapy marks a substantive shift in the standard of care.