Fenebrutinib Shows Remarkable Efficacy in Treating Relapsing MS Patients for 48 Weeks
F. Hoffmann-La Roche Ltd recently released groundbreaking Phase II data demonstrating the exceptional disease suppression capabilities of fenebrutinib in patients with relapsing multiple sclerosis (RMS) for a duration of 48 weeks. The results of the study indicate that the vast majority of patients experienced no relapses or disability progression while being treated with fenebrutinib.
The study, known as the FENopta open-label extension (OLE) study, showcased the ability of fenebrutinib to suppress both acute and chronic MRI lesions in RMS patients. Additionally, the safety profile of fenebrutinib remained consistent with previous and ongoing clinical trials conducted across multiple diseases, with over 2,700 individuals participating in trials to date.
Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development, expressed optimism about the results, stating, “After a year of treatment, our BTK inhibitor fenebrutinib was able to suppress nearly all disease activity and disability progression in people with multiple sclerosis. If these results are validated in the ongoing Phase III trials, fenebrutinib could further advance the treatment landscape for people living with multiple sclerosis.”
Key Findings from the Study:
– 96% of patients treated with fenebrutinib were free of relapses at one year, with an annualised relapse rate of 0.04, and no change in disability over 48 weeks as measured by the Expanded Disability Status Scale (EDSS).
– Fenebrutinib treatment effectively suppressed disease activity in the brain, as evidenced by MRI scans. At 48 weeks, 99% of patients were free of T1 gadolinium-enhancing (T1-Gd+) lesions, which are markers of active inflammation.
– Over the 48-week period of the OLE with continued fenebrutinib treatment, there was a threefold reduction in the volume of T2 lesions, representing chronic disease burden, compared to the end of the double-blind period.
Safety Profile of Fenebrutinib:
The safety profile of fenebrutinib in the OLE study remained consistent with previously reported data. The most common adverse events reported in more than 5% of patients included urinary tract infection (8%), COVID-19 (7%), and pharyngitis (5%). Serious adverse events occurred in only one patient (1%). Additionally, an asymptomatic alanine aminotransferase elevation newly occurred in one patient (1%) but resolved with treatment discontinuation.
Future Prospects:
Three Phase III clinical trials are currently ongoing, including the FENhance 1 and 2 trials in RMS and the FENtrepid trial in primary progressive multiple sclerosis (PPMS). Data from these studies, expected at the end of 2025, will provide further insights into the effects of fenebrutinib on disease progression across the multiple sclerosis spectrum.
About Fenebrutinib:
Fenebrutinib is an investigational oral, reversible, and non-covalent Bruton’s tyrosine kinase (BTK) inhibitor designed to block the function of BTK. BTK plays a crucial role in regulating B-cell development and activation, as well as in the activation of innate immune system myeloid lineage cells such as macrophages and microglia. Preclinical data have highlighted the potency and selectivity of fenebrutinib, making it a promising candidate for the treatment of multiple sclerosis. Notably, fenebrutinib has shown to be 130 times more selective for BTK compared to other kinases, potentially limiting off-target effects and contributing to long-term safety.
The dual inhibitory action of fenebrutinib on both B-cell and microglia activation holds promise in reducing disease activity and disability progression in multiple sclerosis patients. The ongoing Phase III programme includes trials in RMS and PPMS, with fenebrutinib being evaluated against active comparators such as teriflunomide and OCREVUS.
The FENopta Study:
The FENopta study was a global Phase II, randomised, double-blind, placebo-controlled 12-week study aimed at evaluating the efficacy, safety, and pharmacokinetics of fenebrutinib in adults with RMS. The study revealed that fenebrutinib significantly reduced new T1 gadolinium-enhancing lesions and new/enlarging T2 lesions compared to placebo. The safety profile of fenebrutinib remained consistent with previous trials, with no new safety concerns identified.
Furthermore, patients who completed the FENopta study had the option to participate in an open-label extension study, where all patients received fenebrutinib for up to 192 weeks. Ninety-nine patients entered the OLE, with 96 remaining in the study after one year.
About Multiple Sclerosis:
Multiple sclerosis is a chronic disease affecting over 2.9 million individuals globally. The condition arises when the immune system mistakenly attacks the myelin sheath around nerve cells in the central nervous system, leading to inflammation and damage. Symptoms of multiple sclerosis can vary widely and may include weakness, fatigue, and vision problems, eventually progressing to disability. Early diagnosis and treatment are crucial to slowing, stopping, and preventing disease progression.
Relapsing-remitting multiple sclerosis (RRMS) is the most common form of the disease, characterized by episodes of relapses followed by periods of recovery. Most individuals diagnosed with RRMS will transition to secondary progressive multiple sclerosis (SPMS), experiencing worsening disability over time. Primary progressive multiple sclerosis (PPMS) is a debilitating form of the disease with steadily worsening symptoms but typically without distinct relapses.
Roche’s Commitment to Neuroscience:
Neuroscience is a key focus area for Roche, with ongoing research into various neurological disorders including neuromuscular diseases, neuroimmune diseases, and neurodegenerative diseases. The company is dedicated to developing innovative treatments that improve the lives of individuals with chronic and debilitating conditions.
Roche’s sustainability efforts have been recognized, with the company named one of the most sustainable pharmaceutical companies by the Dow Jones Sustainability Indices for fifteen consecutive years. Through partnerships and collaborations, Roche aims to provide personalized healthcare solutions and improve access to healthcare globally.
In conclusion, the Phase II data on fenebrutinib’s efficacy in treating relapsing multiple sclerosis patients for 48 weeks is highly promising. The results indicate significant disease suppression, minimal relapses, and no disability progression in the majority of patients. With ongoing Phase III trials and a focus on advancing treatment options for multiple sclerosis, Roche is at the forefront of neuroscience research and innovation.