Roche had its New Drug Application accepted by the US FDA under priority review on September 30, 2026, for investigational fenebrutinib in relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS).
The application is based on the Phase III FENhance 1 and 2 studies in RMS and Phase III FENtrepid study in PPMS. Fenebrutinib is an oral, CNS-penetrant, reversible, non-covalent Bruton's tyrosine kinase (BTK) inhibitor designed to inhibit both B-cell-mediated peripheral inflammation and microglial activity within the central nervous system.
In FENhance 1 and 2, fenebrutinib reduced annualized relapse rate by 51.1% and 58.5%, respectively, versus teriflunomide over 96 weeks, while also reducing active and chronic brain lesions. Roche reported consistent positive trends favoring fenebrutinib on measures of disability progression.
In FENtrepid, fenebrutinib met the primary endpoint of non-inferiority to ocrelizumab (Ocrevus) on 12-week composite confirmed disability progression in PPMS. Fenebrutinib produced a numerical 12% reduction in progression risk versus ocrelizumab (HR 0.88; 95% CI 0.75–1.03), but did not establish superiority.
Teriflunomide is FDA-approved for relapsing MS, while ocrelizumab is approved for both relapsing MS and PPMS and remains the only FDA-approved therapy specifically for PPMS. Among other oral BTK programs, Novartis reported positive Phase III RMS results for remibrutinib in September 2026 and plans global regulatory submissions. Sanofi's tolebrutinib, marketed as Cenrifki, was approved in the EU in June 2026 for secondary progressive MS without relapses in the previous two years.