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Fenebrutinib in PPMS

Posted on November 25, 2025 by
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Roche announced in early Oct that their BTKi (Bruton’s Tyrosine Kinase inhibitor) was non-inferior to ocrelizumab (anti-B-cell) in PPMS.

In a pivotal PPMS study (FENtrepid), fenebrutinib slowed disability progression at least as effectively as OCREVUS, the only approved therapy in PPMS [Ad hoc announcement pursuant to Art. 53 LR]

This was measured by a delay in the onset of composite confirmed disability progression over a period of at least 120 weeks of treatment.
A numerical benefit for fenebrutinib compared to ocrelizumab was seen as early as week 24, and lasted throughout the observation period.

The trial design is important to understand in this context. A non-inferiority trial, such as this one, is structured to determine whether fenebrutinib is not worse than an established therapy, in this case, ocrelizumab within a predefined margin. In other words, the aim is to show that fenebrutinib could be considered a viable alternative or replacement for the current standard treatment, not that it performs better. It is therefore crucial to recognise that a non-inferiority trial does not provide evidence of superiority. This is why I am somewhat confused by the final statement suggesting there was a “numerical benefit.” Without access to the full dataset (which I expect will likely be presented at the Spring AAN meeting) it is difficult to interpret what is meant by this or assess the clinical relevance. What is clear, however, is that these treatments represent two fundamentally different therapeutic classes, and having an additional option available when one therapy is unsuitable or ineffective can only benefit patients.

Source: multiple-sclerosis-research.org

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