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Fenebrutinib: an experimental oral BTK inhibitor under US review for MS

Published by MyelinWatch:

Organisation
Roche
Study sponsor
F. Hoffmann-La Roche Ltd

Fenebrutinib · Fenebrutinib is an oral drug that blocks Bruton’s tyrosine kinase (BTK), an enzyme involved in immune-cell signalling. Three Phase 3 studies tested it in relapsing MS or primary progressive MS: FENhance 1 and 2 compared it with teriflunomide, while FENtrepid compared it with ocrelizumab.

What is the approach?

Fenebrutinib is an oral inhibitor of Bruton’s tyrosine kinase (BTK), a protein involved in B-cell and other immune-cell signalling. Researchers test whether altering this signalling can limit MS activity and disability progression; the mechanism does not itself establish clinical benefit or myelin repair.

Approach source: Roche — fenebrutinib development announcement ↗

What is being studied

Fenebrutinib is an oral drug that blocks Bruton’s tyrosine kinase (BTK), an enzyme involved in immune-cell signalling. Three Phase 3 studies tested it in relapsing MS or primary progressive MS: FENhance 1 and 2 compared it with teriflunomide, while FENtrepid compared it with ocrelizumab.

Research stage

Large study to confirm benefit and safety

The study continues without taking new participants.

What we know so far

Roche reported 51.1% and 58.5% lower annualised relapse rates than teriflunomide in FENhance 1 and 2 over 96 weeks. Disability findings in those studies were favourable trends, not established superiority on disability. FENtrepid met its noninferiority comparison with ocrelizumab for disability progression: it was not worse by more than the study's pre-set margin (hazard ratio 0.88; 95% confidence interval 0.75–1.03). This does not establish superiority. Roche also reported more liver-enzyme elevations with fenebrutinib in FENtrepid and an imbalance in the number of deaths between treatment arms across the trials. These are sponsor-reported results, and the safety findings need careful assessment.

What this means for patients today

According to Roche, the FDA accepted a US new drug application for Priority Review on 30 September 2026. This is a review step, not approval or proof of availability. The cited sources do not establish authorisation or access in Greece. The three cited trials are listed as active but not accepting new participants.

How BTK inhibitors fit into MS treatment history →

Treatment or approach
Fenebrutinib • experimental oral BTK inhibitor for relapsing and primary progressive MS
How it is intended to work
Oral Bruton’s tyrosine kinase (BTK) inhibitor
Where the study is running
US regulatory application; the cited sources do not establish Greek authorisation or access
Source: Roche — official company announcement ↗Source: Roche — FENhance 1 and 2 relapsing MS results and safety ↗ Source: Roche — FENtrepid primary progressive MS noninferiority results and safety ↗ Source: ClinicalTrials.gov — FENhance 1 (NCT04586010) ↗ Source: ClinicalTrials.gov — FENhance 2 (NCT04586023) ↗ Source: ClinicalTrials.gov — FENtrepid (NCT04544449) ↗
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Programme updates — newest research developments first

  1. US new drug application accepted for FDA Priority Review, according to RocheResearch event/source date:

    Fenebrutinib: Roche says FDA accepted MS application for priority review

    On 30 September 2026, Roche announced that the US FDA had accepted its new drug application for investigational fenebrutinib, an oral BTK inhibitor, for relapsing and primary progressive multiple sclerosis under Priority Review. The application draws on three Phase 3 studies. Roche reported annualised relapse rates 51.1% and 58.5% lower than with teriflunomide in FENhance 1 and 2 over 96 weeks. In FENtrepid, fenebrutinib met the prespecified noninferiority comparison with ocrelizumab for disability progression: it was not worse by more than the study's pre-set margin. The reported hazard ratio was 0.88 (95% confidence interval 0.75–1.03).

    Source: Roche — official company announcement ↗Source: Roche — FENhance 1 and 2 relapsing MS results and safety ↗ Source: Roche — FENtrepid primary progressive MS noninferiority results and safety ↗ Source: ClinicalTrials.gov — FENhance 1 (NCT04586010) ↗ Source: ClinicalTrials.gov — FENhance 2 (NCT04586023) ↗ Source: ClinicalTrials.gov — FENtrepid (NCT04544449) ↗