Sanofi revealed data from a failed Phase 3 trial of the BTK inhibitor tolebrutinib in primary progressive multiple sclerosis (PPMS), detailing why the program missed endpoints and prompting strategic reassessment. At ACTRIMS26 the company’s investigators outlined trial results and contributing factors, including patient selection and disease heterogeneity, that likely influenced the negative outcome. Sanofi’s retreat from this PPMS indication follows the unsuccessful readout. The disclosure highlights the challenges for BTK inhibition in progressive MS and reinforces the need for mechanistic clarity and optimized trial design in neuroimmunology development programs.