At a Glance
Fenebrutinib matched OCREVUS in slowing disability in PPMS.
Disability risk was reduced by 12%, with early benefit at 24 weeks.
Upper limb function showed the strongest improvement.
Safety profile was similar to OCREVUS.
Regulatory filings planned after final Phase III readout.
Written By: Samiksha Jadhav, BPharm
Reviewed By: Pharmacally Editorial Team
Roche has reported encouraging late-breaking Phase III data for its investigational Bruton’s tyrosine kinase (BTK) inhibitor fenebrutinib, positioning the oral therapy as a potential new option for people living with primary progressive multiple sclerosis (PPMS).
Results from the pivotal FENtrepid study (NCT04544449) showed that fenebrutinib met its primary endpoint of non-inferiority versus OCREVUS (ocrelizumab), the only approved treatment for PPMS, in reducing disability progression.
The study also suggested a numerical advantage, with a 12% reduction in the risk of disability progression compared with OCREVUS, as measured by time to 12-week composite confirmed disability progression (cCDP12). Separation between treatment curves was observed as early as week 24 and remained consistent throughout the study period.
Measuring disability more comprehensively
The cCDP12 endpoint combined three validated measures:
Expanded Disability Status Scale (EDSS) for overall functional disability
Timed 25-Foot Walk (T25FW) for walking speed
Nine-Hole Peg Test (9HPT) for upper limb function
Fenebrutinib demonstrated its strongest effect on upper limb function, reducing the risk of confirmed worsening on the 9HPT by 26% compared with OCREVUS. Benefits were consistent across patient subgroups and over the full duration of treatment.
Professor Amit Bar-Or, Director of the Center for Neuroinflammation and Neurotherapeutics at the Perelman School of Medicine, University of Pennsylvania, noted that the early and sustained effect on upper limb function is clinically meaningful, given its role in maintaining independence and daily activities for people with PPMS.
Post-hoc superiority signal
In a post-hoc analysis, fenebrutinib was statistically superior to OCREVUS on a composite endpoint incorporating two components of cCDP12 (EDSS and 9HPT). This analysis showed a 22% reduction in risk of disability progression, further supporting the drug’s potential impact on progressive disease biology.
Safety profile
Overall safety findings for fenebrutinib were broadly comparable with OCREVUS. Common adverse events included infections, nausea, and haemorrhage. Transient and reversible liver enzyme elevations occurred more frequently with fenebrutinib, but all cases resolved after treatment discontinuation, and no Hy’s law cases were reported. Rates of serious adverse events were similar between treatment groups, and fatalities observed in the study were assessed as unrelated to study treatment.
A potential milestone for PPMS
Levi Garraway, Roche’s Chief Medical Officer and Head of Global Product Development, described the results as a potential scientific breakthrough for the PPMS community, highlighting that fenebrutinib is the first therapy in over a decade to show meaningful benefit against the only approved PPMS treatment in a head-to-head study.
The findings were presented as a late-breaking oral session at the Americas Committee for Treatment and Research in Multiple Sclerosis Forum 2026 in San Diego.
Path Forward for Fenebrutinib
The FENtrepid data follow Roche’s November 2025 announcement that both FENtrepid and one of two Phase III relapsing multiple sclerosis studies (FENhance 2, NCT04586023) met their primary endpoints. Roche plans to submit data from all Phase III fenebrutinib trials to regulatory authorities once the second RMS study, FENhance 1 (NCT04586010), reports results in the first half of 2026.
If approved, fenebrutinib could become the first oral, CNS-penetrant BTK inhibitor to offer people with PPMS a new disease-modifying option, targeting both peripheral immune activity and chronic inflammation within the brain.
Reference
Roche’s fenebrutinib is the first investigational medicine in over a decade that reduces disability progression in primary progressive multiple sclerosis (PPMS), 07 February 2026, Roche’s fenebrutinib is the first investigational medicine in over a decade that reduces disability progression in primary progressive multiple sclerosis (PPMS)
A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared with Ocrelizumab in Adult Participants with Primary Progressive Multiple Sclerosis (FENtrepid), ClinicalTrials.gov ID NCT04544449, https://clinicaltrials.gov/study/NCT04544449
A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Teriflunomide in Relapsing Multiple Sclerosis (RMS) (FENhance), ClinicalTrials.gov ID NCT04586010, https://clinicaltrials.gov/study/NCT04586010
Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared with Teriflunomide in Relapsing Multiple Sclerosis (RMS) (FENhance 2), ClinicalTrials.gov ID NCT04586023, https://clinicaltrials.gov/study/NCT04586023