Roche reports Phase III data showing fenebrutinib significantly reduced relapse rates and MRI disease activity in relapsing multiple sclerosis versus teriflunomide.
Written By: Nikita Jha, BPharm
Reviewed By: Pharmacally Editorial Team
Roche has reported positive Phase III results for fenebrutinib in relapsing multiple sclerosis (RMS), demonstrating significant reductions in relapse rates compared with teriflunomide over 96 weeks in the FENhance 1 (NCT04586010) and 2 trials (NCT04586023).
The studies met their primary endpoint, with annualised relapse rate reductions of 51.1% and 58.5%, respectively (p<0.001 and p<0.0001), which Roche stated corresponds to a substantial extension in relapse-free intervals.
Treatment effects were consistent across patient subgroups and were more pronounced in individuals with higher inflammatory activity, including those with active brain lesions, younger age, and earlier-stage disease.
Fenebrutinib also significantly reduced MRI markers of disease activity, with reductions of up to 77.6% in T1 gadolinium-enhancing lesions and up to 82.5% in new or enlarging T2 lesions compared with teriflunomide, indicating suppression of both acute inflammation and chronic lesion burden.
Although the trials were not powered for disability outcomes, secondary analyses showed numerical reductions in 12-week confirmed disability progression of 20% and 13% across the two studies, with greater effects observed in overall and upper-limb disability measures.
These findings are consistent with results from the Phase III FENtrepid study in primary progressive multiple sclerosis, where fenebrutinib demonstrated non-inferiority to OCREVUS in slowing disability progression.
The safety profile was broadly comparable to teriflunomide, including similar rates of liver enzyme elevations, infections, and serious adverse events. However, an imbalance in fatalities was observed, with seven deaths reported in the fenebrutinib arms compared with one in the comparator group, with causes including infections, comorbid conditions, and accidental injury.
Fenebrutinib is an oral, non-covalent, reversible Bruton’s tyrosine kinase inhibitor designed to target both peripheral B cells and central nervous system microglia, allowing it to address inflammatory and neurodegenerative components of multiple sclerosis. Its ability to cross the blood–brain barrier and its high selectivity are intended to support central nervous system activity while limiting off-target effects.
Commenting on the findings, Jiwon Oh, MD, PhD, indicated that fenebrutinib’s dual mechanism may provide a differentiated approach by targeting disease processes in both the periphery and central nervous system, and highlighted that it is the first BTK inhibitor to show superiority in reducing relapses and new brain lesions in Phase III RMS trials with liver safety comparable to a first-line therapy.
Levi Garraway, MD, PhD, Roche’s Chief Medical Officer, stated that the results support the potential of fenebrutinib to extend relapse-free periods and help preserve long-term function in patients.
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About the Writer
Nikita Jha, BPharm a pharmacy graduate specializing in medical writing, with a strong ability to interpret complex medical and regulatory information and translate it into clear, accurate, and evidence-based healthcare content. Known for her attention to detail and precision, she focuses on delivering high-quality scientific communication that supports drug safety and informed decision-making.