Roche reports breakthrough phase III results for investigational multiple sclerosis drug

Fenebrutinib targets cells in the immune system known as B cells and microglia

Swiss pharma giant Roche has announced a major milestone in multiple sclerosis (MS) research today as its investigational oral drug fenebrutinib achieved pivotal success in two Phase III clinical trials.

In patients with relapsing MS (RMS), fenebrutinib significantly reduced relapse rates compared with teriflunomide, while in primary progressive MS (PPMS), the therapy demonstrated non-inferiority to OCREVUS (ocrelizumab) in slowing disability progression. The results suggest fenebrutinib could emerge as a first-in-class, high-efficacy oral treatment for both RMS and PPMS, offering new hope to millions living with MS, the pharma giant said.

“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, 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," he added.

Liver safety was consistent with previous fenebrutinib studies. Additional safety data is being further evaluated. The results of the second RMS Phase III trial (FENhance 1) are expected by the first half of 2026.

Fenebrutinib targets cells in the immune system known as B cells and microglia. Targeting B cells helps control the acute inflammation that causes relapses, while targeting microglia inside the brain addresses the chronic damage that is thought to drive long-term disability progression, Roche said.

Fenebrutinib, a non-covalent BTKi, is designed to have high potency, selectivity and reversibility. This design allows it to act throughout the body, and also to cross the blood-brain barrier into the central nervous system (CNS) targeting chronic inflammation.

During the trial, eligible participants -- 1,497 adult patients -- were randomised 1:1 to receive treatment with either oral fenebrutinib twice a day (and placebo matched to oral teriflunomide once a day) or oral teriflunomide once a day (and placebo matched to oral fenebrutinib twice a day) for at least 96 weeks.

The primary endpoint is annualised relapse rate (ARR). Key secondary endpoints include the time to onset of composite 24-week confirmed disability progression (cCDP24), 12-week confirmed disability progression (CDP12) and 24-week confirmed disability progression (CDP24).

Following the double-blind treatment period, patients have the option to enter an open-label extension (OLE) phase, in which all patients receive treatment with fenebrutinib.