Fenebrutinib for Multiple Sclerosis Returns Significant Phase III Results
Key Clinical Summary
- Fenebrutinib, an investigational Bruton’s tyrosine kinase (BTK) inhibitor, significantly reduced annualized relapse rate (ARR) in relapsing multiple sclerosis (RMS) versus teriflunomide in the Phase III FENhance 1 study.
- FENhance 1 and FENhance 2 together show consistent relapse reductions of 51% and 59%, respectively.
- Full dataset, including results for primary progressive MS (PPMS), will be submitted to regulators; detailed data will be presented at the American Academy of Neurology (AAN) Annual Meeting 2026.
Roche Group announced on Sunday, March 1, that its pivotal Phase III FENhance 1 trial of fenebrutinib met its primary endpoint in relapsing multiple sclerosis (RMS), demonstrating statistically significant and clinically meaningful reductions in relapse activity. The results mark the third positive Phase III study in its comprehensive MS development program.
Fenebrutinib is designed as a non-covalent, Bruton’s tyrosine kinase (BTK) inhibitor targeting both peripheral B cells and microglia in the central nervous system (CNS) to address both acute inflammatory relapses and chronic progression.
Study Findings
The FENhance 1 Phase III trial enrolled adult patients with RMS across multiple international sites to compare investigational fenebrutinib, a BTK inhibitor, against teriflunomide. Over at least 96 weeks, fenebrutinib reduced the annualized relapse rate (ARR) by 51% compared to teriflunomide. These findings align with the previously reported 59% ARR reduction in the FENhance 2 study.
Secondary endpoints also showed statistically significant, clinically meaningful reductions in magnetic resonance imaging (MRI)-measured brain lesions. Additionally, all progression endpoints demonstrated favorable trends for fenebrutinib. Full datasets from both FENhance studies are scheduled for presentation at the American Academy of Neurology (AAN) Annual Meeting 2026 and, along with data from the FENtrepid study in primary progressive MS (PPMS), will be submitted to regulatory authorities.
Safety results indicated that liver transaminase elevations were comparable between treatment arms. There was one Hy’s Law case each in the fenebrutinib and teriflunomide arms, both asymptomatic and resolving after discontinuation. There was 1 fatality in the teriflunomide arm and 8 fatalities in the fenebrutinib arm. Analyses of causes are ongoing.
Clinical Implications
The FENhance 1 results support fenebrutinib’s potential as a high-efficacy oral treatment for multiple sclerosis, with activity in both relapsing and progressive disease biology—an unmet clinical need. Current disease-modifying therapies often require injections or infusions, and efficient oral alternatives with CNS penetration could enhance patient adherence and quality of life.
Clinicians should note the consistency of ARR reductions across FENhance 1 and 2, and the pending regulatory submission underscores industry momentum toward expanding oral options in MS care. The inclusion of MRI lesion reductions strengthens the evidence for fenebrutinib’s disease-modifying effects beyond relapse control. Furthermore, the program’s inclusion of PPMS data may inform future treatment paradigms for a patient population with limited options. Safety findings, particularly regarding liver enzymes and rare serious events, will require integration into clinical decision-making if approval pathways advance.
Expert Commentary
“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, MD, PhD, Chief Medical Officer and Head of Global Product Development at Roche. He emphasized Roche’s commitment to advancing MS treatments that could help people “live a life without disability.”
Reference
Roche’s fenebrutinib confirms its potential as first and only BTK inhibitor for relapsing and primary progressive MS in third positive phase III study (FENhance 1). News release. F. Hoffman-La Roche Ltd. Published online March 1, 2026. Accessed March 4, 2026.
