Sanofi’s Cenrifki (tolebrutinib) has received EU approval as the first therapy to slow disability progression in non-relapsing secondary progressive multiple sclerosis, supported by Phase 3 HERCULES data.
Written By: Kalyani Boharapi,
M.Pharm (Reg. Affairs)
Reviewed By: Pharmacally Editorial Team
Sanofi has received European Commission approval for Cenrifki (tolebrutinib) to treat adults with secondary progressive multiple sclerosis (SPMS) who have not experienced relapses during the previous two years. The decision makes Cenrifki the first therapy approved in the European Union specifically to target disability progression in non-relapsing SPMS, a patient population with limited treatment options.
The approval follows a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) and is supported by results from the Phase 3 HERCULES trial, with additional evidence from the Phase 3 GEMINI 1 and GEMINI 2 studies.
Addressing a Major Unmet Need in SPMS
Multiple sclerosis is a chronic autoimmune disease that damages the central nervous system. Many patients eventually transition to SPMS, a stage marked by steady worsening of neurological function, mobility limitations, cognitive decline, fatigue, and increasing loss of independence.
Unlike relapsing forms of the disease, non-relapsing SPMS is driven largely by chronic inflammation within the brain and spinal cord that continues even in the absence of acute relapses. Treatment options capable of slowing disability progression have remained limited.
Cenrifki is an oral, once-daily Bruton’s tyrosine kinase (BTK) inhibitor that penetrates the central nervous system and targets smoldering neuroinflammation, a key biological driver of disability accumulation in multiple sclerosis.
HERCULES Trial Showed Significant Delay in Disability Progression
The European approval is primarily based on findings from the Phase 3 HERCULES study (NCT04411641), which evaluated tolebrutinib in patients with non-relapsing SPMS.
The double-blind trial randomized participants in a 2:1 ratio to receive either oral tolebrutinib or placebo for up to approximately four years. Eligible patients had documented disability worsening during the previous year, no relapses for at least 24 months, and Expanded Disability Status Scale (EDSS) scores ranging from 3.0 to 6.5.
The study met its primary endpoint, demonstrating that tolebrutinib significantly delayed six-month confirmed disability progression compared with placebo. Secondary endpoints assessed disability worsening over three months, disability improvement, MRI lesion activity, upper-limb function, walking performance, and overall safety.
Supporting evidence came from the Phase 3 GEMINI 1 (NCT04410978) and GEMINI 2 (NCT04410991) trials, which compared tolebrutinib with teriflunomide in patients with relapsing multiple sclerosis. These studies further strengthened the overall clinical evidence package reviewed by European regulators.
Safety Profile Requires Ongoing Liver Monitoring
Sanofi reported a safety profile that remained consistent across the clinical development program.
The most commonly reported adverse events included COVID-19 infection and upper respiratory tract infections. Investigators also observed clinically significant elevations in liver enzymes.
Drug-induced liver injury (DILI) has been identified as an important safety risk associated with Cenrifki. As a result, treatment requires strict liver monitoring and prompt management of liver enzyme abnormalities to reduce the risk of serious hepatic complications.
Treatment should be initiated and supervised by physicians experienced in the management of multiple sclerosis.
Commercial Launch Planned in Germany
Sanofi plans to make Cenrifki available in Germany later this year, supported by a dedicated risk management framework and patient support program. The company will work closely with MS specialists to facilitate the therapy’s introduction into clinical practice.
Cenrifki has already received approvals in Australia and the United Arab Emirates for specific SPMS indications. With the EU authorization now secured, Sanofi has established the first approved treatment specifically targeting the underlying processes that drive disability accumulation in non-relapsing SPMS, potentially reshaping care for patients facing progressive neurological decline.
What This Means for Patients
For people living with non-relapsing secondary progressive multiple sclerosis (SPMS), Cenrifki offers a new treatment option that targets the underlying processes driving disability progression rather than focusing solely on relapse control. Many patients continue to experience worsening mobility, fatigue, cognitive impairment, and loss of independence even after relapses stop, with few therapies available to slow this decline. By delaying confirmed disability progression in the Phase 3 HERCULES study, Cenrifki may help patients maintain physical function and independence for longer. However, treatment requires regular liver monitoring due to the risk of drug-induced liver injury, and patients should discuss the potential benefits and risks with their treating neurologist.
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About the Writer
Kalyani Boharapi (LinkedIn) is a pharmacy professional and healthcare writer currently pursuing an M.Pharm in Regulatory Affairs at Dr. D. Y. Patil College of Pharmacy, with interests in pharmaceutical regulations, drug development, and healthcare innovation. She has academic exposure to dossier preparation, scientific writing, and regulatory documentation. Kalyani has also completed certification courses in Generative AI, AI in Pharma, and Bioinformatics, and actively participates in pharmaceutical conferences to stay updated with emerging trends and advancements in the healthcare and pharmaceutical industry.