Roche with good interim clinical results

Roche’s Bruton thyrosine kinase inhibitor fenebrutinib, which previously failed in Phase II trials in arthritis and SLE patients, appears to help patients with relapsing forms of multiple sclerosis. This is suggested by interim results from a non-blinded small extension of the Phase II FenOpta study with 70 treated patients, which Roche AG will present at the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Copenhagen, Denmark on 18 September 2024.

The results show that patients with relapsing forms of multiple sclerosis (RMS) treated with fenebrutinib for up to one year have very low disease activity and no progression of disability. “If these results are confirmed in ongoing Phase III trials, fenebrutinib could further improve the treatment landscape for people with multiple sclerosis,” hopes Dr Levi Garraway, Roche’s Chief Medical Officer and Head of Global Product Development.

During the 40 week open-label extension period, 96% of patients treated with fenebrutinib were free of relapses at one yearas measured by the Expanded Disability Status Scale (EDSS). During the previous 12-week FenOpta study, at weeks 4, 8 and 12 (combined), fenebrutinib patients had a 69% reduction in total new Gd+ lesions and a 74% reduction in total NET2 lesions vs placebo patients..

The safety profile of fenebrutinib in the OLE was consistent with previously reported data. The most common adverse events (AEs) in >5% of patients were urinary tract infection (8%), COVID-19 (7%) and pharyngitis (5%). Serious AEs occurred in one patient (1%). In the open label extension, an asymptomatic alanine aminotransferase elevation occurred newly in one patient (1%) and resolved with treatment discontinuation. In December, the FDA had discntinued the Phase III FENhance study, due to transaminase elevations in two patients that pointed to a potential drug-induced ADE.

Three Phase III clinical trials are ongoing, including the FENhance 1 and 2 trials in RMS and the FENtrepid trial in primary progressive multiple sclerosis (PPMS). Data from these studies, which will characterise the effects of fenebrutinib on disease progression across the multiple sclerosis spectrum, are expected at the end of 2025.

Fenebrutinib is a pyrimidine-based, reversible and non-covalent Bruton’s tyrosine kinase (BTK) inhibitor that  inhibits both B-cell and microglia activation. This dual inhibition may be able to reduce both multiple sclerosis disease activity and disability progression.. The fenebrutinib Phase III programme includes two identical trials in relapsing multiple sclerosis (RMS) (FENhance 1 & 2) with active comparator teriflunomide and the only trial in primary progressive multiple sclerosis (PPMS) (FENtrepid) in which a BTK inhibitor is being evaluated against Ocrevus.