Sanofi’s tolebrutinib (branded Cenrifki) cleared another step for multiple sclerosis in Europe after the FDA had issued a complete response letter in the U.S. for treatment of non-relapsing secondary progressive MS. The EMA’s CHMP adopted a positive opinion for approval in the EU for patients without relapses in the previous two years. The CHMP recommendation is based on the Hercules phase III trial in nrSPMS and supported by the Gemini 1 and Gemini 2 phase III studies in relapsing MS. If approved, Cenrifki would be an oral, brain-penetrant Bruton’s tyrosine kinase inhibitor aimed at smoldering neuroinflammation linked to disability progression. Industry impact: the divergent U.S.-EU trajectory highlights how regulators can weigh safety and clinical benefit packages differently by region, shaping development resubmission strategies and commercial planning for BTK inhibitors in progressive MS.