Written By: Pharmacally Medical News Desk
Roche has announced exceptional positive results from late-stage Phase III clinical trials of fenebrutinib, an investigational oral Bruton’s tyrosine kinase (BTK) inhibitor, in both relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS). These results mark a pivotal milestone, positioning fenebrutinib as potentially the first and only BTK inhibitor to demonstrate efficacy across the full MS disease spectrum, offering hope for millions living with MS worldwide.
Study Design and Trials
The Phase III program for fenebrutinib includes two pivotal trials for RMS FENhance 1 (NCT04586023) and 2 (NCT04586010) and the FENtrepid trial (NCT04544449) for PPMS. FENhance 2, the first RMS trial to report results, was a randomized, double-blind, double-dummy study comparing fenebrutinib to teriflunomide over 96 weeks of treatment, with annualized relapse rate (ARR) as the primary endpoint. The FENtrepid trial in PPMS compared fenebrutinib to ocrelizumab (Ocrevus), the only approved therapy for PPMS, evaluating disability progression over 120 weeks.
Key Efficacy Results
In the FENhance 2 trial, fenebrutinib significantly reduced the ARR compared to teriflunomide, demonstrating superior control of relapses in RMS. In PPMS, fenebrutinib showed non-inferiority to ocrelizumab in delaying confirmed disability progression, with numerical benefits appearing as early as week 24 and sustained through 120 weeks. These findings underscore fenebrutinib’s ability to address both inflammation and progression in MS, a unique feature enabling it to target B cells and microglia by crossing the blood-brain barrier.
Safety Profile
Fenebrutinib demonstrated a consistent safety profile across trials. Liver-related adverse events were comparable to earlier studies and manageable within the clinical settings. Further detailed safety data are under evaluation, with no new major safety concerns reported to date.
About Fenebrutinib
Fenebrutinib is an investigational oral Bruton’s tyrosine kinase (BTK) inhibitor developed by Roche/Genentech, distinct for its high selectivity, reversibility, and ability to penetrate the central nervous system (CNS) by crossing the blood-brain barrier.
BTK is a crucial intracellular enzyme involved in signaling pathways that regulate B lymphocytes and myeloid cells, including microglias, which are resident immune cells in the CNS. Both B cells and microglia contribute to the inflammatory and neurodegenerative processes in MS. By inhibiting BTK, fenebrutinib aims to reduce peripheral inflammation driven by B cells as well as the compartmentalized CNS inflammation mediated by microglia, which may contribute to disease progression and disability in MS.
Next Steps and Regulatory Plans
Roche expects to release the results of the FENhance 1 trial in the first half of 2026, after which it plans to consolidate data for regulatory submissions globally. If approved, fenebrutinib would fulfill a significant unmet need, being the first oral high-efficacy treatment for both RMS and PPMS, potentially reshaping MS treatment paradigms.
Key Opinion
Levi Garraway, MD, PhD, Roche’s Chief Medical Officer, emphasized fenebrutinib potential as a “best-in-disease” medicine for MS, highlighting its efficacy and oral dosing advantage. These groundbreaking results may provide new hope to patients by addressing both acute relapses and the progressive disabling aspects of MS, ultimately improving quality of life.
References
Roche’s fenebrutinib shows unprecedented positive Phase III results as the potential first and only BTK inhibitor in both relapsing and primary progressive multiple sclerosis, 10 Nov 2025, Roche, https://www.roche.com/media/releases/med-cor-2025-11-10
A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Teriflunomide in Relapsing Multiple Sclerosis (RMS) (FENhance), ClinicalTrials.gov ID NCT04586010, https://clinicaltrials.gov/study/NCT04586010