Fenebrutinib cuts multiple sclerosis relapses by 55% as Roche results show slower brain volume loss
Key Facts
Roche said in a statement issued on October 21, 2026 that its investigational drug fenebrutinib reduced the annualized relapse rate in patients with relapsing multiple sclerosis by 55% compared with teriflunomide over 96 weeks in a pooled analysis of the FENhance trials. The randomized, double-blind trials together enrolled 1,497 adults with the relapsing form of the disease in a head-to-head comparison of the treatments. The proportion of fenebrutinib recipients with no evidence of disease activity was 75%, based on a measure combining the absence of relapses, disease activity on imaging and worsening disability. The analysis also showed a 16% reduction in composite confirmed disability progression compared with teriflunomide. This finding was based on disability progression confirmed over 12 weeks, with a p-value of 0.04, according to the company.
The new findings extended to brain volume and chronic active lesions, with Roche saying fenebrutinib reduced annual whole-brain volume loss by 23% compared with teriflunomide in the pooled analysis. In pivotal studies of the relapsing and primary progressive forms, the drug reduced the volume of slowly expanding lesions by up to 30% versus comparator treatments. This finding covered patients with both forms targeted by the drug's clinical program. Among patients with relapsing multiple sclerosis, the reduction in the accumulation of paramagnetic rim lesions was 62% compared with the comparator treatment. The chronic active lesion findings thus covered the volume of slowly expanding lesions and the accumulation of paramagnetic rim lesions, alongside the finding on whole-brain volume loss.
Fenebrutinib is an investigational oral BTK inhibitor, according to Roche's description of the drug in its regulatory statement. It acts through a non-covalent, reversible mechanism and can cross the blood-brain barrier to reach the central nervous system. Its mechanism targets B cells, which the company links to the acute inflammation that causes relapses in patients with multiple sclerosis. It also targets microglia associated with chronic damage believed to drive disability progression. Roche thus links the drug's mechanism to cells associated with both relapses and chronic damage, two aspects addressed by its clinical program for the relapsing and primary progressive forms.
In the FENtrepid trial in patients with primary progressive multiple sclerosis, Roche said fenebrutinib met the "primary non-inferiority endpoint" compared with Ocrevus in reducing disability progression. In the trial results, the company reported liver enzyme elevations in 13.3% of fenebrutinib recipients, compared with 2.9% of Ocrevus recipients. It described these elevations as transient and reversible, and said the cases resolved after treatment was stopped. The rate of fatal cases in the fenebrutinib group was 1.4% during the trial. In the Ocrevus group, the corresponding rate was 0.2%, and investigators assessed all fatal cases as unrelated to study treatment, according to Roche's statement.
In the trials of the relapsing form, Roche's April disclosure included an imbalance in deaths between the treatment groups during the reporting period. The fenebrutinib group recorded 7 deaths, equivalent to 0.9% of participants in the group. By comparison, the teriflunomide group recorded 1 death, or 0.1%, during the same period. Roche added in the same disclosure that "an additional death was observed after this period." The additional death was mentioned after the presentation of the death toll in the treatment groups in the relapsing-form studies, alongside the drug's reported efficacy results.
On the regulatory front, Roche announced on September 30, 2026 that the U.S. Food and Drug Administration had accepted the application for fenebrutinib for priority review. The application covers the drug's use in treating relapsing multiple sclerosis. It also covers treatment of the primary progressive form, in which the drug was tested against Ocrevus in the FENtrepid trial. Fenebrutinib remains an investigational treatment during the U.S. regulatory review process. In its October statement, the company scheduled the presentation of the chronic active lesion results at the multiple sclerosis congress in Toronto on October 23, 2026.