Roche's fenebrutinib is the first investigational medicine in over a decade that reduces disability progression in primary progressive multiple sclerosis (PPMS)

Core Insights - Roche announced that fenebrutinib, an investigational BTK inhibitor, met its primary endpoint of non-inferiority compared to OCREVUS in reducing disability progression in patients with primary progressive multiple sclerosis (PPMS), showing a 12% reduction in risk of disability progression [1][5] - The treatment effect was consistent across patient subgroups and observed as early as 24 weeks, particularly benefiting upper limb function [3][5] Study Details - The FENtrepid study was a Phase III multicenter, randomized, double-blind trial involving 985 adult patients with PPMS, comparing daily oral fenebrutinib to intravenous OCREVUS for at least 120 weeks [7] - The primary endpoint was the time to onset of 12-week composite confirmed disability progression (cCDP12), which included measures of functional disability, walking speed, and upper limb function [8] Treatment Efficacy - Fenebrutinib demonstrated a 26% reduction in the risk of worsening upper limb function compared to OCREVUS [2] - A post-hoc analysis indicated fenebrutinib was superior to OCREVUS on a composite endpoint including two components of cCDP12, with a 22% reduction in risk [3] Safety Profile - Adverse events in the fenebrutinib group were comparable to OCREVUS, with infections occurring in 67.0% of patients on fenebrutinib versus 70.9% on OCREVUS [4] - Transient liver enzyme elevations were more common in the fenebrutinib group (13.3% vs 2.9% for OCREVUS), but all cases resolved after discontinuation of the drug [4] Future Developments - Roche plans to submit regulatory applications for fenebrutinib in both PPMS and relapsing multiple sclerosis (RMS) following the readout of the second pivotal RMS study, FENhance 1, expected in mid-2026 [5][6]