Roche’s Fenebrutinib Reduces Relapse Rate By 51% In Phase III FENhance 1 Trial For Relapsing Multiple Sclerosis

Roche announced that its pivotal Phase III FENhance 1 trial evaluating fenebrutinib in relapsing multiple sclerosis (RMS) achieved its primary endpoint. The investigational Bruton’s tyrosine kinase (BTK) inhibitor reduced the annualised relapse rate (ARR) by 51% compared with teriflunomide over a minimum treatment duration of 96 weeks. These findings align with those from FENhance 2, which demonstrated a 59% reduction in ARR. Collectively, the data suggest patients on fenebrutinib may experience approximately one relapse every 17 years. Secondary endpoints across both RMS trials also showed statistically significant reductions in brain lesions, while progression measures demonstrated favourable trends.

The positive FENhance 1 outcome builds on previously reported successes from FENhance 2 in RMS and FENtrepid in primary progressive multiple sclerosis (PPMS). Together, the three pivotal studies indicate that fenebrutinib may deliver consistent benefits across both relapsing and progressive forms of multiple sclerosis, targeting underlying disease biology.

“These pivotal results, together with the earlier data,  provide convincing evidence that fenebrutinib can become the first high-efficacy oral treatment for RMS and PPMS,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “Building on a decade of transforming MS treatment, we are committed to advancing innovation to one day allow people with MS to live a life without disability.”

Regarding safety, liver transaminase elevations in both RMS trials were comparable between fenebrutinib and teriflunomide. In FENhance 1, one Hy’s Law case occurred in each treatment arm; both were asymptomatic and resolved after discontinuation of therapy. No additional Hy’s Law cases have been observed across the broader fenebrutinib development program in multiple sclerosis or other autoimmune diseases. However, mortality data showed one fatal case in the teriflunomide arm and eight fatal cases in the fenebrutinib arms, with various causes and at different treatment stages. Further evaluation of these findings is ongoing.

Fenebrutinib is a non-covalent BTK inhibitor designed for potency, selectivity, and reversibility. By targeting B cells, it aims to control acute inflammatory relapses, while its ability to cross the blood-brain barrier allows it to act on microglia in the central nervous system, potentially addressing chronic inflammation associated with long-term disability progression.