At the ACTRIMS Forum 2026, Professor Amit Bar-Or presented results from the Phase III FENtrepid study, demonstrating that the BTK inhibitor Fenebrutinib is the first investigational medicine in over a decade to show reduced disability progression in Primary Progressive Multiple Sclerosis (PPMS). Fenebrutinib met its primary endpoint of non-inferiority compared to OCREVUS, with a 12% numerical reduction in risk of disability progression, particularly benefiting upper limb function. Key details from the FENtrepid study presentation include:
- Trial Design: FENtrepid (NCT04544449) was a Phase III, randomized, double-blind study comparing daily oral fenebrutinib to intravenous OCREVUS (ocrelizumab) in PPMS patients.
- Primary Endpoint: Fenebrutinib met the primary endpoint of non-inferiority in reducing 12-week composite confirmed disability progression (cCDP12).
- Clinical Impact: Fenebrutinib showed consistent clinical benefit, including improvements in upper limb function as early as 24 weeks.
- Mechanism: As an oral, brain-penetrant BTK inhibitor, fenebrutinib targets both peripheral immune cell activation and microglial activation within the central nervous system.
- Future Outlook: Following these results, regulatory submissions for fenebrutinib in PPMS and relapsing multiple sclerosis (RMS) are planned for 2026.