Global pharma giant Roche has unveiled late-breaking Phase III data showing its investigational oral therapy fenebrutinib slowed disability progression in people with primary progressive multiple sclerosis, matching—and in some measures outperforming—the only approved treatment for the disease.

 

Results from the Phase III FENtrepid study showed fenebrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, met its primary endpoint of non-inferiority versus OCREVUS (ocrelizumab) in reducing disability progression in patients with primary progressive multiple sclerosis (PPMS). 

 

Fenebrutinib reduced the risk of disability progression by 12% compared with OCREVUS, based on time to 12-week composite confirmed disability progression (cCDP12), with treatment curves separating as early as 24 weeks.

 

The primary endpoint combined three measures of worsening disability: the Expanded Disability Status Scale (EDSS), the timed 25-foot walk (T25FW), and the nine-hole peg test (9HPT), which assesses upper-limb function. The strongest effect was seen in upper-limb function, where fenebrutinib cut the risk of worsening on the 9HPT by 26% 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 the treatment effect on the primary endpoint was consistent across patient subgroups and maintained throughout the full treatment period. In a post-hoc analysis, fenebrutinib also proved superior to OCREVUS on a composite endpoint combining EDSS and 9HPT, reducing the risk of progression by 22%.

 

“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, 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 results were broadly comparable between the two treatments. Common adverse events in the fenebrutinib group included infections, nausea and haemorrhage, at rates similar to OCREVUS. 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. Serious adverse events were reported at similar rates in both treatment arms.

 

In the FENtrepid study, fatal cases occurred in 1.4% of patients receiving fenebrutinib and 0.2% of those receiving OCREVUS. Investigators determined all deaths were unrelated to study treatment, with no pattern observed in timing or cause. Roche noted that epidemiological studies show higher fatality rates among people living with multiple sclerosis compared with the general population.

 

The results follow Roche’s November 2025 announcement that both FENtrepid and the Phase III relapsing multiple sclerosis study FENhance 2 met their primary endpoints. Roche plans to submit data from all Phase III fenebrutinib trials to regulators after the second relapsing MS study, FENhance 1, reports results in the first half of 2026.