Sanofi disclosed data from a failed Phase 3 trial of the BTK inhibitor tolebrutinib in primary progressive multiple sclerosis (PPMS), prompting the company to retreat from that indication. The company and the trial’s lead investigator identified factors that likely contributed to the negative readout presented at ACTRIMS26. The disclosure forces Sanofi to re-evaluate its BTK clinical strategy in progressive MS and may affect investor expectations for other BTK assets. Sponsors and investigators will analyze subgroup and biomarker data to determine if any patient subsets derived benefit and whether different endpoints or designs could salvage development.