Fenebrutinib Reduces Disability Progression in PPMS

In a significant development for the multiple sclerosis (MS) community, Roche has announced that its investigational oral drug, fenebrutinib, has successfully met its primary endpoint in a Phase III trial. The study, known as FENtrepid, marks the first time in over a decade that a new medicine has shown a reduction in disability progression for patients with primary progressive multiple sclerosis (PPMS).

The FENtrepid study evaluated fenebrutinib, a brain-penetrant Bruton’s tyrosine kinase (BTK) inhibitor, against OCREVUS (ocrelizumab), which is currently the only approved treatment for PPMS. Results presented at the ACTRIMS Forum 2026 showed that fenebrutinib was non-inferior to OCREVUS, reducing the risk of 12-week confirmed disability progression by 12%. Notably, the treatment curves began to separate as early as 24 weeks into the trial.

Researchers highlighted the drug's impact on upper limb function, a critical factor for patient independence. Data indicated a 26% reduced risk of worsening in the nine-hole peg test (9HPT) compared to the standard of care. Professor Amit Bar-Or noted that this consistent clinical benefit is essential for "preserving independence and daily functioning" in patients.

Unlike many existing BTK inhibitors that form permanent bonds, fenebrutinib is designed to be reversible, which may help limit off-target effects. While the study reported that common adverse events were comparable to OCREVUS, transient liver enzyme elevations were more frequent in the fenebrutinib group (13.3% vs. 2.9%). Fatal cases were numerically higher in the fenebrutinib arm (1.4% vs. 0.2%), though investigators assessed these as unrelated to the study treatment.

Roche plans to submit these findings to regulatory authorities in mid-2026, following the results of the FENhance 1 trial for relapsing MS. If approved, fenebrutinib could become a first-in-class, high-efficacy oral treatment option that directly targets the chronic damage driving long-term disability.

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🔖 Sources

 Roche’s fenebrutinib is the first investigational medicine in over a decade that reduces disability progression in primary progressive multiple sclerosis (PPMS)

Roche’s fenebrutinib demonstrates decade-first benefit in multiple sclerosis

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Keywords: Fenebrutinib Reduces Disability Progression

Fenebrutinib Reduces Disability Progression

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