Sanofi disclosed detailed results from a failed Phase 3 trial of the BTK inhibitor tolebrutinib in primary progressive multiple sclerosis (PPMS). The company’s presentation at ACTRIMS highlighted why the study missed endpoints and prompted Sanofi to retreat from that particular indication. Investigators pointed to trial design and disease heterogeneity as contributing factors. The disclosure underscores the challenges of translating BTK inhibition into progressive MS and will influence go/no‑go calculus for other BTK programs in neuroimmunology.