Roche announced that its investigational oral Bruton’s tyrosine kinase (BTK) inhibitor, fenebrutinib, met the primary endpoint in the Phase III FENtrepid study for primary progressive multiple sclerosis (PPMS).
The trial demonstrated non-inferiority compared to the only currently approved therapy for PPMS, Ocrevus, with fenebrutinib reducing the risk of disability progression by 12% as early as 24 weeks. The strongest effect was observed in upper limb function, with a 26% reduction in risk of worsening.
FENtrepid is a multicentre, randomised, double-blind Phase III trial involving 985 adult PPMS patients, using a 12-week composite confirmed disability progression (cCDP12) endpoint. The composite captures total functional disability, walking speed, and upper limb function, providing greater sensitivity than standard measures alone. Patients have the option to continue in an open-label extension phase after the double-blind period.
Fenebrutinib, an oral, brain-penetrant BTK inhibitor, is designed to target both relapsing and progressive biology in multiple sclerosis by modulating B cells and microglia. The drug’s selectivity and reversible binding profile aim to maximize efficacy while limiting off-target effects. Roche’s Phase III programme also includes two relapsing MS trials (FENhance 1 and 2) comparing fenebrutinib to teriflunomide.
Common adverse events observed were comparable to Ocrevus, including infections, nausea, and hemorrhage. Liver enzyme elevations were transient and resolved on discontinuation, with no cases of severe liver injury reported.
Following completion of the FENhance 1 relapsing MS trial, Roche plans to submit regulatory filings for fenebrutinib in both PPMS and relapsing MS during the first half of 2026. The therapy could become a first-in-class oral treatment option for MS, addressing a decade-long gap in disease-modifying therapies for PPMS.
