Roche's Fenebrutinib Shows Promise in Treating Relapsing Multiple Sclerosis in Early Study Results

Roche’s Bruton’s tyrosine kinase inhibitor, fenebrutinib, which had previously not met expectations in Phase II trials for arthritis and systemic lupus erythematosus (SLE), is now showing promise in treating relapsing forms of multiple sclerosis (RMS). This potential is indicated by interim findings from a small, open-label extension of the Phase II FenOpta study involving 70 patients. Roche AG plans to present these findings at the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Copenhagen on September 18, 2024.

The interim results suggest that RMS patients treated with fenebrutinib for up to one year experienced very low disease activity and no progression in disability. Dr. Levi Garraway, Roche’s Chief Medical Officer and Head of Global Product Development, noted that if these results are confirmed in ongoing Phase III trials, fenebrutinib could significantly advance treatment options for multiple sclerosis.

During the 40-week open-label extension, 96% of patients on fenebrutinib were relapse-free at one year, as measured by the Expanded Disability Status Scale (EDSS). In the initial 12-week FenOpta study, fenebrutinib treatment resulted in a 69% reduction in total new Gd+ lesions and a 74% reduction in total NET2 lesions compared to placebo.

The safety profile of fenebrutinib in the extension study aligned with previously reported data. Common adverse events (AEs) included urinary tract infections (8%), COVID-19 (7%), and pharyngitis (5%). Serious AEs were reported in just one patient (1%). Notably, an asymptomatic elevation in alanine aminotransferase was observed in one patient, resolving after discontinuation of treatment. In December, the FDA halted the Phase III FENhance study due to transaminase elevations in two patients, raising concerns about potential drug-induced adverse effects.

Currently, three Phase III trials are ongoing: FENhance 1 and 2 for RMS, and FENtrepid for primary progressive multiple sclerosis (PPMS). These studies are expected to provide comprehensive data on fenebrutinib’s impact on disease progression across the multiple sclerosis spectrum by the end of 2025.

Fenebrutinib is a reversible, non-covalent Bruton’s tyrosine kinase (BTK) inhibitor that targets both B-cell and microglia activation. This dual action could potentially reduce both disease activity and disability progression in multiple sclerosis. The Phase III program includes two identical trials in RMS (FENhance 1 & 2) with an active comparator, teriflunomide, and a trial in PPMS (FENtrepid), where fenebrutinib is being evaluated against Ocrevus.