Roche’s Genentech announced this week that its phase 2 trial evaluating its relapsing multiple sclerosis (RMS) Bruton tyrosine kinase (BTK) inhibitor drug, fenebrutinib, had met all its primary and secondary endpoints.
The trial, called FENopta, is a 12-week, randomized, double-blind, placebo-controlled study that includes 109 patients with RMS. The study’s overall goal was to asses the impact of fenebrutinib on disease activity and progression using MRI and soluble biomarkers, with an optional substudy to measure cerebrospinal fluid biomarkers of neuronal injury.
FENopta’s primary endpoint focused on the total number of new gadolinium-enhancing T1 lesions observed through MRI scans of the brain at 4, 8, and 12 weeks, and its secondary endpoints included reducing the number of new or enlarging T2-weighted lesions and the proportion of patients free from new lesions, as assessed by MRI scans.
In the trial, fenebrutinib demonstrated a significant reduction in new gadolinium-enhancing T1 brain lesions compared to placebo, and significantly reduced the number of new or enlarging T2 brain lesions. Also, a higher proportion of fenebrutinib-treated patients remained free from new gadolinium-enhancing T1 brain lesions and new or enlarging T2-weighted brain lesions compared to those on placebo. MRI measurements of T1 lesions indicate active inflammation, while T2 lesions reflect the extent of disease burden or lesion load.
The drug’s phase 3 program includes two trials in relapsing MS, with an active teriflunomide comparator and in primary progressive MS comparing fenebrutinib to Genentech's humanized anti-CD20 monoclonal antibody Ocrevus.
BTK inhibitors have run up against some issues recently. Earlier this year, Biogen abandoned its deal with InnoCare Pharma involving a BTK inhibitor candidate being studied as a potential MS treatment. Last month, the FDA placed a partial clinical hold on ongoing phase 3 trials of evobrutinib, Merck KGaA’s experimental BTK inhibitor for relapsing forms of MS, following reports of elevated liver enzymes.
