Fenebrutinib cuts multiple sclerosis relapses by 58.5% versus teriflunomide in Roche trial
Key Facts
Fenebrutinib reduced the annualised relapse rate in patients with relapsing multiple sclerosis by 58.5% compared with teriflunomide in the FENhance 2 trial, according to detailed results Roche announced in April 2026. The relative reduction was 51.1% in FENhance 1, which also compared the drug with teriflunomide in patients with the relapsing form of the disease. The reported percentages refer to the annualised relapse rate compared with the treatment used in the trials' comparator groups. The company said in its disclosure that fenebrutinib also reduced "chronic disease burden" compared with teriflunomide. Roche measured that burden using new or enlarging T2 lesions. The results were part of a programme studying the drug's effect on relapses in patients with the relapsing form and on disability progression in patients with the primary progressive form.
The FENhance trials together enrolled 1,497 adults with relapsing multiple sclerosis, according to Roche's March 2026 disclosure on the clinical programme. The studies were conducted at multiple centres using a randomised, parallel-group design to compare the treatments. They used double-blind and double-dummy methods, according to the company's description of the trials testing the drug's efficacy and safety. In FENhance 1, fenebrutinib is administered as tablets taken orally twice daily, according to Roche's patient-facing study page. Eligibility criteria for this trial specified patients aged between 18 and 55. The page required participants to have relapsing multiple sclerosis, the form targeted by the comparison with teriflunomide in the FENhance trials.
Fenebrutinib's mechanism targets B cells and microglia, according to Roche's explanation of how the drug works in its September 2026 disclosure. The company links B cells to the inflammation that causes relapses in people with multiple sclerosis. It links microglia to the chronic damage associated with disability progression in patients. Roche announced in October 2023 that data from the early FENopta trial showed fenebrutinib could cross the blood-brain barrier. It said at the time that this ability offered the potential to act directly on chronic inflammation within the central nervous system and supported the scientific rationale for targeting it with the drug. In an estimate of the disease's prevalence, the company said in its September disclosure that multiple sclerosis is a chronic disease affecting more than 3 million people worldwide.
In patients with primary progressive multiple sclerosis, the FENtrepid trial met its primary endpoint of demonstrating non-inferiority to Ocrevus in reducing disability progression, according to Roche. The company described the result as meeting the "primary non-inferiority endpoint" in the comparison between the treatments. Results from this trial also included a disclosure of liver enzyme elevations during treatment. In results announced in February 2026, the proportion of participants with these elevations was 13.3% with fenebrutinib, compared with 2.9% with Ocrevus. Roche described the liver enzyme elevations as transient and reversible, occurring more frequently in the fenebrutinib group than in the Ocrevus group. It added that all cases resolved after the study drug was discontinued in affected participants.
In the safety disclosure accompanying the detailed results in April 2026, Roche announced an imbalance in reported deaths across the studies. The company said "an imbalance in reported deaths was observed across the studies" as part of its presentation of the clinical programme's results. The trials in the relapsing form recorded 7 deaths among participants receiving fenebrutinib during the reporting period. In the comparator group receiving teriflunomide, 1 death was recorded during the same period, according to the figures provided by the company. Roche said the deaths occurred at different times and from various causes across the studies. The disclosure accompanied the efficacy results the company announced for the drug in the trials in the relapsing form.
On the regulatory front, Roche announced on 30 September 2026 that the U.S. Food and Drug Administration had accepted fenebrutinib's application for priority review. The application covers treatment of relapsing multiple sclerosis and the primary progressive form, according to the company's statement on the drug's regulatory pathway. The announced action is acceptance of the application for priority review, with the drug remaining investigational. Regarding participant follow-up, the FENhance programme includes an open-label extension after the double-blind treatment period ends. According to Roche's March 2026 statement, participants can enter this phase after completing that period of the study. All patients entering the open-label extension receive fenebrutinib, under the arrangement the company announced for continuing the programme.