On Monday, Roche Holdings AG disclosed recent data from the pivotal Phase 3 FENtrepid study, evaluating fenebrutinib, an investigational oral Bruton's tyrosine kinase (BTK) inhibitor, designed to target progressive multiple sclerosis (MS) and other autoimmune conditions. Fenebrutinib is distinguished by its high selectivity and reversible, non-covalent action against BTK, and crucially it crosses the blood-brain barrier, enabling it to modulate B-cell and microglial activity within the central nervous system to reduce inflammation.
This update follows Roche's prior announcements in November 2025, affirming that FENtrepid and one of two Phase 3 relapsing multiple sclerosis (RMS) trials, FENhance 2, met their primary endpoints. The outcome of the second RMS study, FENhance 1, remains pending with data anticipated in the first half of 2026, after which comprehensive submissions to regulatory bodies based on all Phase 3 fenebrutinib trials will be pursued.
Primary Endpoint Achievement and Clinical Impact
The FENtrepid trial succeeded in meeting its main objective of demonstrating non-inferiority to Ocrevus (ocrelizumab), the only approved medication for primary progressive multiple sclerosis (PPMS), in reducing disability progression. Specifically, fenebrutinib showed a 12% reduction in risk relative to Ocrevus, as assessed by the composite confirmed disability progression over 12 weeks (cCDP12). Notably, divergence in the progression curves became apparent as early as 24 weeks into treatment.
The treatment benefit on cCDP12 was consistent throughout the patient subgroups evaluated and maintained over the entire treatment duration. The cCDP12 endpoint integrates measures from three assessments: the Expanded Disability Status Scale (EDSS), capturing functional disability; the timed 25-foot walk (T25FW), evaluating walking speed; and the nine-hole peg test (9HPT), assessing upper limb function.
The most substantial improvement with fenebrutinib compared to Ocrevus was observed in the 9HPT component, where the risk of worsening was reduced by 26%. This outcome suggests a pronounced effect on upper limb function, a critical area impacting patient independence and daily activities.
Expert Commentary and Significance
Professor Amit Bar-Or, leading the Center for Neuroinflammation and Neurotherapeutics at the University of Pennsylvania's Perelman School of Medicine, emphasized the clinical relevance of these findings. He highlighted that fenebrutinib exhibited consistent benefits as early as week 24, especially in preserving upper limb capabilities fundamental for autonomy in PPMS patients.
Roche's Chief Medical Officer and Global Product Development Head, Levi Garraway, characterized fenebrutinib as the first potential scientific advance for the PPMS community in more than ten years. He underlined its role as a high-efficacy oral therapeutic option, working directly within the brain to target progressive disease mechanisms and potentially slow the advancement of disability.
Supplementary post-hoc analysis indicated that fenebrutinib statistically outperformed Ocrevus on a composite endpoint encompassing two of the three cCDP12 components: the EDSS and 9HPT. This analysis showed a 22% reduction in progression risk favoring fenebrutinib.
Next Steps and Data Sharing
The results from the FENtrepid study were publicly presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2026. Roche is advancing with preparations to submit regulatory filings once the second RMS study results become available, which will provide a complete data package from all Phase 3 fenebrutinib studies for evaluation.
In market response, Roche's shares closed higher by 1.02% to $57.70, reflecting measured investor interest following these data disclosures.