FDA gives priority review to Roche’s oral BTK inhibitor fenebrutinib for relapsing MS and primary progressive MS

# What happened

# What fenebrutinib is designed to do Fenebrutinib is an oral inhibitor of Bruton's tyrosine kinase (BTK), a protein involved in the activity of B cells and other immune cells implicated in MS. Blocking BTK is intended to reduce two types of inflammation: the acute inflammation that causes relapses and the chronic, smoldering inflammation inside the brain that contributes to gradual disability progression.

# Evidence supporting the filing The application is supported by three ongoing Phase 3 trials:

• FENhance 1 and FENhance 2: These twin trials enrolled nearly 1,500 adults with relapsing MS. Fenebrutinib reduced the average number of relapses per year by more than 50% compared with teriflunomide (Aubagio). Roche reported that relapse rates in those trials equated to roughly one relapse every 17 years, and fenebrutinib also cut new and enlarging MRI lesions and lesions with active inflammation by over 70%. The trials showed a positive trend toward slower disability progression.

• FENtrepid: This trial compared fenebrutinib with ocrelizumab (Ocrevus) in adults with PPMS. Fenebrutinib was at least as effective as ocrelizumab and produced a numerical 12% reduction in the risk of confirmed disability progression vs ocrelizumab. The study detected treatment effects even in patients without MRI signs of active inflammation.

Roche describes these results as evidence that fenebrutinib can target both relapse activity and progression across MS types.

# What Roche officials said

# Why this matters to patients and clinicians An oral therapy that demonstrates high efficacy on relapse metrics and shows potential effects on progression could expand treatment options, especially for patients seeking alternatives to infusions. The reported reductions in relapse rates and MRI lesion counts are clinically relevant markers used in MS practice. The signal on disability progression in PPMS is notable because fewer treatments have demonstrated effects there, and some existing therapies benefit primarily patients with active inflammation on MRI.

# Next steps and timeline With priority review, the FDA aims to reach a decision within approximately six months. Roche's filing makes fenebrutinib the first BTK inhibitor accepted for FDA review for both relapsing MS and PPMS. Pending an approval decision in spring 2027, clinicians and patients will need to review the full FDA assessment and Roche's final labeling for safety details, recommended use, and any monitoring requirements.