Roche Reports Positive Phase III Results for Fenebrutinib in Multiple Sclerosis

Roche announced that its investigational Bruton’s tyrosine kinase (BTK) inhibitor fenebrutinib met key efficacy goals across multiple phase III studies in multiple sclerosis (MS).

The FENhance 2 trial, the first of two pivotal, similarly designed phase III studies in relapsing multiple sclerosis (RMS), achieved its primary endpoint. Fenebrutinib significantly reduced the annualized relapse rate (ARR) compared with teriflunomide after at least 96 weeks of treatment.

In addition, the FENtrepid phase III trial in primary progressive multiple sclerosis (PPMS) met its main goal, showing that fenebrutinib was non-inferior to Ocrevus (ocrelizumab)—currently the only approved PPMS therapy—in delaying confirmed disability progression over 120 weeks. A numerical benefit for fenebrutinib compared with Ocrevus was observed as early as week 24 and persisted throughout the study.

“Fenebrutinib substantially reduced relapses in RMS and slowed disability progression in PPMS,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “These results suggest that fenebrutinib could potentially become the first high-efficacy, oral treatment for both RMS and PPMS.”

Liver safety findings were consistent with earlier studies, and additional safety evaluations are ongoing. Results from the second RMS trial, FENhance 1, are expected in the first half of 2026.

Dual Mechanism Targeting B Cells and Microglia

Fenebrutinib acts on B cells and microglia, two immune cell types implicated in MS progression. By targeting both peripheral inflammation and chronic neuroinflammation in the brain, the drug aims to reduce relapses and long-term disability.

Fenebrutinib is a non-covalent, reversible BTK inhibitor with high potency and selectivity, designed to cross the blood–brain barrier and modulate immune activity within the central nervous system (CNS).

Overview of the Clinical Program

• FENhance 1 & 2: Phase III, randomized, double-blind trials comparing oral fenebrutinib with teriflunomide in 1,497 RMS patients.
  - Primary endpoint: Annualized relapse rate (ARR).
  - Secondary endpoints: 12-week and 24-week confirmed disability progression.
  - Duration: Minimum of 96 weeks.
• FENtrepid: Phase III, double-blind trial comparing daily oral fenebrutinib with intravenous Ocrevus in 985 PPMS patients over at least 120 weeks.
  - Primary endpoint: 12-week composite confirmed disability progression (cCDP12).
  - The composite measure combines assessments of walking speed, upper limb function, and overall disability.

All participants completing the blinded phase were offered enrollment in an open-label extension to continue fenebrutinib treatment.

Background on Multiple Sclerosis

Multiple sclerosis affects more than 2.9 million people globally. About 85% have a relapsing form, while 15% are diagnosed with PPMS, characterized by steady progression without relapses. Despite advances, slowing or preventing disability progression remains a central challenge in MS care.

Roche’s Broader Neuroscience Focus

Roche continues to expand its neuroscience portfolio, investigating therapies for MS, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and other neurological conditions. The company aims to develop treatments that address both disease activity and progression.

Founded in 1896 in Basel, Switzerland, Roche is the world’s largest biotechnology company and a global leader in in-vitro diagnostics, committed to advancing science that improves and saves lives.

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