Roche has announced new late-breaking data from the phase III FENtrepid trial showing that its investigational Bruton’s Tyrosine Kinase (BTK) inhibitor, fenebrutinib, met the primary endpoint of non-inferiority versus Ocrevus (ocrelizumab) in patients with Primary Progressive Multiple Sclerosis (PPMS).

The study demonstrated a 12 percent reduction in the risk of disability progression compared to Ocrevus, currently the only approved therapy for PPMS. The primary endpoint, time to onset of 12-week composite confirmed disability progression (cCDP12), showed a hazard ratio (HR) of 0.88 (95 percent), with separation of treatment curves observed as early as week 24. A consistent treatment effect was seen across patient subgroups and throughout the treatment period.

The composite endpoint incorporated measures of disability including the Expanded Disability Status Scale (EDSS), timed 25-foot walk (T25FW), and nine-hole peg test (9HPT). Notably, fenebrutinib demonstrated a 26 percent reduction in the risk of worsening upper limb function as measured by the 9HPT (HR 0.74; 95 percent) compared to Ocrevus.

A post-hoc analysis further showed superiority over Ocrevus on a composite endpoint comprising EDSS and 9HPT, with a 22 percent reduction in risk (HR 0.78; 95 percent).

Professor Amit Bar-Or from the University of Pennsylvania highlighted that fenebrutinib showed consistent clinical benefit early in treatment, particularly in preserving upper limb function, a key factor in maintaining independence for patients with PPMS.

Roche’s Chief Medical Officer, Levi Garraway, described the findings as a potential scientific breakthrough for the PPMS community, marking the first significant development in over a decade. The company plans to proceed with regulatory submissions following the anticipated readout of the second pivotal relapsing MS (RMS) trial, FENhance 1, expected in the first half of 2026.

In terms of safety, adverse events were generally comparable between fenebrutinib and Ocrevus. Common events included infections, nausea and haemorrhage. Elevated liver enzymes were more frequent in the fenebrutinib group (13.3 percent vs 2.9 percent) but were transient and resolved after discontinuation. No Hy’s law cases were reported. Serious adverse events occurred in 19.1 percent of fenebrutinib-treated patients compared to 18.9 percent in the Ocrevus arm. Fatal cases were higher numerically in the fenebrutinib group, but investigators determined these were unrelated to study treatment.

The FENtrepid study enrolled 985 adults with PPMS and compared daily oral fenebrutinib to intravenous Ocrevus over at least 120 weeks in a randomised, double-blind design. Patients completing the double-blind phase may enter an open-label extension.

Fenebrutinib is an oral, CNS-penetrant, reversible and non-covalent BTK inhibitor designed to target both peripheral B cells and microglia in the central nervous system. By inhibiting acute inflammatory processes and chronic neurodegenerative pathways, it aims to address both relapsing and progressive disease biology.

Results were presented as a late-breaking oral session at the ACTRIMS Forum 2026 in San Diego. Pending additional data from the ongoing phase III RMS programme, Roche intends to submit the full clinical package to regulatory authorities.