Roche has reported late-breaking phase 3 data showing that its investigational Bruton’s tyrosine kinase (BTK) inhibitor fenebrutinib met the primary endpoint in a head-to-head study against OCREVUS (ocrelizumab) in patients with primary progressive multiple sclerosis (PPMS), a form of the disease with limited treatment options.
Results from the FENtrepid trial, presented February 7 at the ACTRIMS Forum 2026 in San Diego, showed that fenebrutinib was non-inferior to OCREVUS in reducing disability progression, as measured by the time to 12-week composite confirmed disability progression (cCDP12). Fenebrutinib also demonstrated a numerical 12% reduction in the risk of disability progression compared with OCREVUS, with treatment curves separating as early as 24 weeks.
OCREVUS is currently the only approved disease-modifying therapy for PPMS. Fenebrutinib is an oral, brain-penetrant BTK inhibitor that Roche is developing for both progressive and relapsing forms of multiple sclerosis.
The primary endpoint in FENtrepid combined three measures of disability: functional disability using the Expanded Disability Status Scale (EDSS), walking speed assessed by the timed 25-foot walk, and upper limb function measured by the nine-hole peg test. According to Roche, treatment effects were consistent across patient subgroups and over the duration of the study.
The strongest treatment effect was observed in upper limb function, with fenebrutinib reducing the risk of worsening on the nine-hole peg test by 26% compared with OCREVUS. Upper limb impairment is a key driver of loss of independence in people with progressive MS and is not always well captured by traditional disability measures.
A post-hoc analysis further suggested superiority for fenebrutinib on a composite endpoint including EDSS and upper limb function, showing a 22% reduction in the risk of progression 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 Amit Bar-Or, director of the Center for Neuroinflammation and Neurotherapeutics at the University of Pennsylvania, in a statement.
Safety findings were generally comparable between treatment arms. Common adverse events included infections, nausea and haemorrhage. Transient and reversible liver enzyme elevations occurred more frequently with fenebrutinib than with OCREVUS, though no cases met criteria for severe drug-induced liver injury. Serious adverse events were reported at similar rates in both groups, and investigators assessed all reported deaths as unrelated to study treatment.
FENtrepid enrolled 985 adults with PPMS and followed patients for at least 120 weeks in a randomized, double-blind, double-dummy design. Participants received either daily oral fenebrutinib or intravenous OCREVUS, along with matched placebos.
The data follow Roche’s November 2025 announcement that FENtrepid and one of two phase 2 relapsing MS studies met their primary endpoints. Roche plans to submit regulatory filings for fenebrutinib in both PPMS and relapsing MS after results from the second relapsing MS study, FENhance 1, which are expected in the first half of 2026.
If approved, fenebrutinib could become the first oral therapy shown to reduce disability progression in PPMS.
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