Roche’s fenebrutinib accepted for FDA priority review for RMS and PPMS

Regulatory status

The US FDA has accepted Roche’s New Drug Application for fenebrutinib under priority review for both relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS), based on a Phase III clinical programme.

Phase III efficacy data

Two RMS studies (FENhance 1 and 2) reported annualised relapse rate reductions of 51.1% and 58.5% versus teriflunomide over 96 weeks, equating in the report to roughly one relapse every 17 years. The PPMS trial (FENtrepid) met its primary endpoint of non-inferiority versus ocrelizumab, showing a numerical 12% reduction in time to confirmed 12‑week composite disability progression (HR 0.88; 95% CI 0.75–1.03) with separation of curves from about 24 weeks and consistent effects across subgroups, including patients without active inflammation.

Safety profile

Across the pivotal studies, rates of serious adverse events differed by trial: FENhance 1 (9% fenebrutinib; 9% teriflunomide), FENhance 2 (11% fenebrutinib; 6% teriflunomide) and FENtrepid (19% fenebrutinib; 19% ocrelizumab). Liver enzyme elevations were comparable to teriflunomide in RMS studies and observed more often versus ocrelizumab in PPMS. An imbalance in reported fatalities was noted across studies; causes and timing varied. The overall safety database covers more than 2,700 participants.

Mechanism and positioning

Fenebrutinib is an oral, CNS‑penetrant, reversible non‑covalent Bruton’s tyrosine kinase (BTK) inhibitor designed to target B cells and microglia to address both acute relapses and chronic CNS inflammation thought to drive disability progression. If approved, it would be the first BTK inhibitor and the first high‑efficacy oral treatment for both RMS and PPMS.