Late-breaking Phase III FENtrepid study results show the investigational oral, brain-penetrant Bruton’s tyrosine kinase (BTK) inhibitor fenebrutinib met its primary endpoint of non-inferiority compared to OCREVUS (ocrelizumab) in reducing disability progression in patients with primary progressive multiple sclerosis (PPMS). Fenebrutinib, a potential first-in-class treatment for PPMS and relapsing multiple sclerosis (RMS), numerically reduced the risk of disability progression by 12% compared to OCREVUS, the only previously approved medicine for PPMS. The primary endpoint measured the time to onset of 12-week composite confirmed disability progression (cCDP12), which includes metrics for functional disability, walking speed, and upper limb function. A consistent treatment effect was observed across patient subgroups, with the strongest effect being a 26% reduction in the risk of worsening upper limb function as measured by the nine-hole peg test (9HPT). A post-hoc analysis further demonstrated that fenebrutinib was superior to OCREVUS on a composite endpoint including EDSS and 9HPT, showing a 22% risk reduction. Common adverse events were comparable between fenebrutinib and OCREVUS, although transient and reversible liver enzyme elevations were more frequent with fenebrutinib. Fenebrutinib is designed to target both acute inflammation by inhibiting B cells and chronic damage by targeting microglia within the central nervous system. Regulatory submission for fenebrutinib in both PPMS and RMS is planned following the readout of the second pivotal RMS study, FENhance 1, expected in the first half of 2026. This data represents a potential scientific breakthrough for the PPMS community, offering a meaningful clinical benefit versus the current standard of care.