Roche’s Fenebrutinib Meets Phase III Endpoints In Relapsing And Progressive Multiple Sclerosis

Roche, announced that its investigational Bruton’s tyrosine kinase (BTK) inhibitor, fenebrutinib, achieved its primary endpoint in the first of two pivotal Phase III trials, FENhance 2, evaluating patients with relapsing multiple sclerosis (RMS). Over a 96-week period, fenebrutinib significantly reduced the annualized relapse rate (ARR) compared to teriflunomide, marking an important milestone in the company’s late-stage MS development program.

In parallel, the FENtrepid Phase III study, which compared fenebrutinib with Roche’s approved therapy OCREVUS® (ocrelizumab) in patients with primary progressive multiple sclerosis (PPMS), also met its primary endpoint. Fenebrutinib demonstrated non-inferiority to ocrelizumab in delaying confirmed disability progression over at least 120 weeks of treatment. Notably, a numerical benefit for fenebrutinib was observed as early as week 24, persisting throughout the study duration, underscoring its potential to address both inflammatory and progressive forms of MS.

“Fenebrutinib substantially reduced the number of relapses in RMS and slowed disability progression in PPMS. These unprecedented results suggest that fenebrutinib could potentially become a best-in-disease medicine as the first high-efficacy, oral treatment for people with RMS or PPMS,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "Therefore, these pivotal results for fenebrutinib may offer new hope for people living with MS, and they reaffirm our enduring commitment to the MS community.”

Liver safety findings were consistent with previous studies, and additional data will be assessed in ongoing analyses. Results from the second RMS trial, FENhance 1, are expected in the first half of 2026. Fenebrutinib is a highly selective, non-covalent BTK inhibitor designed to act both peripherally and within the central nervous system (CNS) by targeting B cells and microglia—two key drivers of acute and chronic inflammation in multiple sclerosis. Its dual mechanism offers a promising new therapeutic approach aimed at reducing relapses and slowing long-term disability progression.