Roche’s Genentech has reported new data from the Phase III FENtrepid trial of fenebrutinib, an investigational Bruton’s tyrosine kinase inhibitor, for treating primary progressive multiple sclerosis (PPMS).
The Phase III trial met its primary endpoint, demonstrating non-inferiority to Ocrevus in reducing disability progression in PPMS patients.
It also showed that fenebrutinib reduced the risk of disability progression by 12% against Ocrevus, which is currently the only approved treatment for PPMS.
This was measured by the time to onset of 12-week composite confirmed disability progression (cCDP12), with a hazard ratio of 0.88. Curves separated as early as 24 weeks, and a consistent effect was observed across patient subgroups and throughout the treatment period.
The cCDP12 endpoint utilised three components: the timed 25-foot walk (T25FW) for walking speed, the nine-hole peg test (9HPT) for upper limb function, and the expanded disability status scale (EDSS) for functional disability.
The most pronounced benefit was seen in the 9HPT, with fenebrutinib reducing the risk of worsening by 26% compared to Ocrevus.
A post-hoc analysis found fenebrutinib superior to Ocrevus on a composite endpoint combining EDSS and 9HPT, with a 22% lower risk.
Adverse events were similar between groups: nausea, haemorrhage, and infections. Transient liver enzyme elevations were more frequent with fenebrutinib, resolving after treatment discontinuation.
Serious adverse events occurred in 19.1% of fenebrutinib patients versus 18.9% with Ocrevus, leading to withdrawal rates of 4.3% and 3.0%, respectively. Fatal cases were seen in 1.4% on fenebrutinib and 0.2% on Ocrevus; none were attributed to treatment.
Following completion of the FENhance 1 study, data from all Phase III trials will be submitted to regulatory authorities.
Roche chief medical officer and global product development head Levi Garraway said: “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.
“We look forward to advancing our regulatory submission following the upcoming readout of our second pivotal RMS study, FENhance 1.”
In June 2025, Roche and Genentech announced outcomes from the randomised, multi-centre, international Phase III SUNMO trial for those with relapsed or refractory LBCL who are ineligible for transplant.
