Roche's Fenebrutinib Nearly Halts Disease Activity in Relapsing MS for 48 Weeks

Roche has disclosed promising new data from the Phase II FENopta open-label extension (OLE) study concerning its Bruton’s tyrosine kinase (BTK) inhibitor, fenebrutinib, intended for patients with relapsing multiple sclerosis (RMS). The data will be presented at the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Copenhagen.

The 48-week study results indicate that patients treated with fenebrutinib maintained low disease activity and showed no signs of disability progression over the course of one year. Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development, remarked on the significant reduction in disease activity and disability progression in patients after one year of treatment. If these results are validated in ongoing Phase III trials, fenebrutinib could become a crucial treatment for multiple sclerosis.

During the OLE period, 96% of patients treated with fenebrutinib experienced no relapses, with an annualized relapse rate (ARR) of 0.04. Moreover, no change in disability was noted over the 48 weeks, as measured by the Expanded Disability Status Scale (EDSS). The treatment also suppressed disease activity in the brain, as MRI scans showed that 99% of patients were free of T1 gadolinium-enhancing (T1-Gd+) lesions, indicative of active inflammation. Additionally, there was a threefold reduction in the volume of T2 lesions, which represent chronic disease burden, compared to the end of the double-blind period.

The safety profile of fenebrutinib in the OLE study was in line with previously reported data. The most common adverse events (AEs) occurring in more than 5% of patients included urinary tract infection (8%), COVID-19 (7%), and pharyngitis (5%). A serious AE was recorded in one patient. An asymptomatic increase in alanine aminotransferase was observed in one patient and resolved upon treatment discontinuation.

Currently, three Phase III clinical trials are underway, including the FENhance 1 and 2 trials for RMS and the FENtrepid trial for primary progressive multiple sclerosis (PPMS). These trials are expected to provide more data on fenebrutinib’s effects on disease progression across the multiple sclerosis spectrum by the end of 2025.

Fenebrutinib is described as an investigational oral, reversible, and non-covalent BTK inhibitor. BTK is an enzyme that plays a role in the development and activation of B-cells and myeloid lineage cells such as macrophages and microglia. The drug is noted for its high selectivity and reversible inhibition, which may contribute to its long-term safety by limiting off-target effects.

Fenebrutinib acts as a dual inhibitor, targeting both B-cell and microglia activation. This mechanism may reduce both disease activity and disability progression in multiple sclerosis patients. The Phase III program for fenebrutinib includes two identical trials in RMS (FENhance 1 & 2) and a trial in PPMS (FENtrepid), making it the only BTK inhibitor being evaluated against OCREVUS for PPMS. Over 2,700 patients and healthy volunteers have been treated with fenebrutinib across different phases of clinical programs for multiple diseases, including multiple sclerosis.

The FENopta study initially involved 109 adults aged 18-55 with RMS. The primary endpoint was the total number of new T1-Gd+ lesions, with secondary endpoints including the number of new or enlarging T2-weighted lesions. The study aimed to characterize fenebrutinib's effect on MRI and soluble biomarkers of disease activity and progression, also including an optional substudy for cerebrospinal fluid analysis. Data indicated that fenebrutinib crossed the blood-brain barrier and significantly reduced new T1-Gd+ and T2 lesions compared to placebo.

Ninety-nine patients continued into the OLE study, with 96 remaining after one year, further reaffirming fenebrutinib's potential in managing multiple sclerosis.

Multiple sclerosis is a chronic disease affecting over 2.9 million people globally. It involves the immune system attacking the central nervous system, leading to various symptoms and potentially resulting in disability. RMS is the most common form, characterized by episodes of relapses and recoveries. Another form, PPMS, involves steadily worsening symptoms without distinct relapses. Early diagnosis and treatment are crucial in managing the disease's progression and improving patient outcomes.