Roche announced late-breaking Phase III data showing that fenebrutinib reduces disability progression in PPMS, marking the first investigational advance for primary progressive multiple sclerosis in more than a decade. Results from the FENtrepid study showed the Bruton’s tyrosine kinase inhibitor met its primary endpoint of non-inferiority versus OCREVUS in delaying confirmed disability progression.
In the study, fenebrutinib demonstrated a 12% reduction in the risk of disability progression compared with OCREVUS, measured by time to 12-week composite confirmed disability progression. Treatment curves separated as early as 24 weeks, with consistent effects observed across patient subgroups and throughout the treatment period.
The primary endpoint combined outcomes from the Expanded Disability Status Scale, the timed 25-foot walk and the nine-hole peg test. The strongest effect was seen in upper limb function, with a 26% reduction in worsening on the nine-hole peg test compared with OCREVUS.
“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.”
Roche said a post-hoc analysis showed fenebrutinib reduces disability progression in PPMS more effectively than OCREVUS on a composite endpoint including functional disability and upper limb performance, with a 22% reduction in risk.
“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 1.”
Safety findings showed adverse events were broadly comparable between fenebrutinib and OCREVUS, with infections, nausea and haemorrhage reported most commonly. Transient liver enzyme elevations occurred more frequently with fenebrutinib but resolved after treatment discontinuation, with no Hy’s law cases reported.
The results were presented as a late-breaking oral session at the ACTRIMS Forum 2026 in San Diego. Roche said full Phase III data will be submitted to regulators once the second relapsing multiple sclerosis study reads out in the first half of 2026.
