Sanofi SA secured regulatory approval in Europe for Cenrifki (tolebrutinib) to treat adults with non-relapsing secondary progressive multiple sclerosis (SPMS), marking the first disability-targeting medicine for this specific patient population in the region. The approval addresses a critical unmet need, though the drug continues to face safety challenges following a rejection by U.S. regulators. The European Commission's decision is supported by results from the Phase 3 HERCULES study, which demonstrated that Cenrifki significantly delayed the onset of disability progression in patients with non-relapsing SPMS.

Clinical Trial Overview

The approval relies on data from three key phase 3 studies evaluating the efficacy and safety of tolebrutinib across different forms of multiple sclerosis.

Safety Profile and Regulatory Challenges

The safety profile of Cenrifki was consistent across the clinical program, with the most common adverse events being COVID-19 and upper respiratory tract infections. However, significant liver enzyme elevations were observed, and drug-induced liver injury (DILI) was identified as a potential safety risk. In December 2025, the U.S. Food and Drug Administration (FDA) issued a complete response letter for the new drug application, determining that the proposed risk evaluation and mitigation strategy could not adequately mitigate the serious risk of severe DILI. Consequently, Sanofi booked a 1.66 billion-euro write-down on tolebrutinib alongside its 2025 results.

Launch Plans and Risk Management

Sanofi plans to make Cenrifki commercially available in Germany later this year. The launch will be supported by a required Risk Management Program and a robust Patient Support Program, involving close collaboration between local medical teams, MS specialists, and patients. Strict adherence to liver monitoring requirements and prompt management of enzyme elevations are necessary to mitigate the risk of liver injury. Cenrifki is an oral, brain-penetrant Bruton's tyrosine kinase inhibitor designed to target smoldering neuroinflammation, a key driver of disability progression.

Additional Regulatory Milestone in Japan

Separately, Japan’s Ministry of Health, Labor and Welfare granted marketing and manufacturing authorization for Wayrilz (rilzabrutinib) for persistent or chronic immune thrombocytopenia (ITP) in patients who have not responded adequately to existing therapies. The approval was based on data from the Phase 3 LUNA 3 trial involving 202 adults, where 23% of patients receiving Wayrilz achieved a durable platelet response at week 25, compared with none in the placebo group.

The Ministry of Health, Labour and Welfare in Japan has granted marketing and manufacturing authorization to Sanofi for Wayrilz (rilzabrutinib) to treat persistent or chronic immune thrombocytopenia (ITP) in adults. This approval addresses a significant unmet need for patients who do not respond sufficiently to other treatments or face tolerability issues. Wayrilz is a novel oral reversible Bruton’s tyrosine kinase inhibitor (BTKi) that works through multi-immune modulation to target key pathways across the immune system.

The regulatory decision is based on the LUNA 3 phase 3 study (clinical study identifier: NCT04562766). In this trial, Wayrilz met the primary and secondary endpoints, demonstrating a positive impact on sustained platelet counts and other symptoms compared to placebo. The study evaluated the efficacy and safety of the drug in adults with persistent or chronic ITP.

LUNA 3 Phase 3 Study Results

The study included 202 adults, with patients eligible to continue the full 24-week double-blind period if they achieved a platelet count response at 12 weeks. Results showed that 64% of patients in the Wayrilz arm continued, compared to 32% in the placebo arm. Key outcomes for patients receiving Wayrilz included:

Patients receiving Wayrilz reported an overall 10.6-point improvement in the quality of life domain, compared to a 2.3-point increase in the placebo arm, based on The Immune Thrombocytopenia Patient Assessment Questionnaire. The most common adverse reactions, with an incidence of 10% or more, were diarrhea, nausea, headache, abdominal pain, and COVID-19.

Future Indications and Designations

Wayrilz is currently being studied across multiple other rare diseases, including IgG4-related disease (IgG4-RD), warm autoimmune hemolytic anemia (wAIHA), and sickle cell disease. These additional indications are under investigation and have not yet received regulatory approval. Japan has granted Wayrilz orphan drug designation for ITP, IgG4-RD, and wAIHA.