Objective:

To evaluate the efficacy of fenebrutinib, an oral BTK inhibitor, compared to OCREVUS in reducing disability progression in patients with primary progressive multiple sclerosis (PPMS).

Key Findings:

• Fenebrutinib was non-inferior to OCREVUS in reducing disability progression.
• A numerical 12% reduction in the risk of disability progression was observed with fenebrutinib compared to OCREVUS.
• The strongest treatment effect was noted in upper limb function, with a 26% reduction in risk of worsening on the nine-hole peg test.
• Post-hoc analysis indicated a 22% reduction in risk of progression on a composite endpoint including EDSS and upper limb function.

Interpretation:

Fenebrutinib demonstrated consistent clinical benefits, particularly in upper limb function, which is crucial for maintaining independence in patients with PPMS.

Limitations:

• Safety findings showed more frequent transient liver enzyme elevations with fenebrutinib, though no severe liver injuries were reported.
• Common adverse events included infections, nausea, and hemorrhage, with similar rates of serious adverse events between groups.

Conclusion:

If approved, fenebrutinib could be the first oral therapy to demonstrate a reduction in disability progression in PPMS, offering a new treatment option for patients.