Roche’s Fenebrutinib Matches OCREVUS In Phase III PPMS Study, Shows Disability-Risk Reduction, Data Highlight Fenebrutinib’s Potential In Progressive Multiple Sclerosis

Roche has reported new late-breaking Phase III results from the FENtrepid trial showing that its investigational Bruton’s tyrosine kinase (BTK) inhibitor, fenebrutinib, achieved non-inferiority to OCREVUS (ocrelizumab) in slowing disability progression in patients with primary progressive multiple sclerosis (PPMS). Fenebrutinib reduced the risk of 12-week composite confirmed disability progression (cCDP12) by 12% compared with OCREVUS, with treatment curves separating as early as 24 weeks and consistent benefits across patient subgroups.

The primary endpoint combined measures from the Expanded Disability Status Scale, the timed 25-foot walk and the nine-hole peg test for upper-limb function. Fenebrutinib showed its strongest effect on hand and arm performance, cutting the risk of worsening on the nine-hole peg test by 26% compared with OCREVUS. A post-hoc analysis also suggested superiority on a composite endpoint including disability score and upper-limb function, translating to a 22% lower risk of progression.

“Fenebrutinib showed a consistent clinical benefit as early as week 24, notably in upper limb function, which is essential for preserving independence and daily functioning,” said Professor Amit Bar-Or, Director of the Center for Neuroinflammation and Neurotherapeutics, Perelman School of Medicine, University of Pennsylvania. “With only one disease-modifying therapy available for people with PPMS, fenebrutinib has the potential to be a high-efficacy, oral treatment option that acts directly in the brain, targeting progressive biology, and may slow disability.”

Safety findings were broadly comparable between treatments. Common adverse events included infections, nausea and haemorrhage, while reversible liver enzyme elevations were more frequent with fenebrutinib and resolved after stopping therapy. Rates of serious adverse events were similar in both arms, and although more deaths occurred in the fenebrutinib group, investigators judged these unrelated to treatment and consistent with the higher background risk seen in people with multiple sclerosis.

“Fenebrutinib represents the first potential scientific breakthrough for the PPMS community in over a decade, demonstrating a meaningful clinical benefit in reducing disability progression in a study versus the only approved treatment in PPMS,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “We look forward to advancing our regulatory submission following the upcoming readout of our second pivotal RMS study, FENhance.”

The data were presented as a late-breaking oral session at ACTRIMS 2026 in San Diego and build on Roche’s earlier announcement that FENtrepid and one relapsing MS study met their primary endpoints. Once results from the remaining Phase III relapsing MS trial become available in the first half of 2026, Roche plans to submit the full fenebrutinib data package to regulators.