Fully enrolled phase III Evobrutinib studies continue
The US Food and Drug Administration (FDA) has placed a partial clinical hold on the initiation of new patients on evobrutinib and patients with less than 70 days exposure to study medication in the US.
12 April 2023: Merck today announced the US Food and Drug Administration (FDA) has placed a partial clinical hold on the initiation of new patients on evobrutinib and patients with less than 70 days exposure to study medication in the US. The ongoing, fully-enrolled Phase III EVOLUTION clinical trial programme of evobrutinib in relapsing multiple sclerosis (RMS) will continue as planned with all participants remaining on treatment as all are beyond 70 days exposure to study medication.
The Phase III clinical trial programme of evobrutinib is on schedule to read out in the fourth quarter of 2023.
The FDA action was based on their assessment of two recently reported cases of laboratory values suggestive of drug-induced liver injury that have been identified during the Phase III studies. Importantly, both patients were asymptomatic, did not require any medical intervention or hospitalisation for this condition and their liver enzymes fully normalised after discontinuation of the study medication.
The Phase III EVOLUTION clinical trial programme of evobrutinib has been closely monitored by an Independent Data Monitoring Committee, including hepatologists, since initiation. In close collaboration with external experts as well as the Independent Data Monitoring Committee for the trials, Merck is assessing the potential contributory role of predisposing factors to the liver injury.
Merck is working closely with the FDA to establish the best path forward for the benefit of patients in current and future trials with evobrutinib.
Evobrutinib is an oral, CNS-penetrating, highly selective inhibitor of Bruton’s tyrosine kinase (BTK) in clinical development as a potential treatment for relapsing multiple sclerosis (RMS). It is the first BTK inhibitor (BTKi) to demonstrate clinical efficacy in the largest Phase II study with follow-up beyond three years as well as demonstrate an impact on early biomarkers of ongoing central inflammation that correlate with disease progression, including slowly expanding lesions (SEL) volume and levels of blood neurofilament light chain protein (NfL). Evobrutinib is designed to modulate B cell responses such as proliferation and antibody and cytokine release, as well as modulate macrophage/microglia activation. During Phase II, the BTKi dose finding study demonstrated that BID dosing achieved maximal efficacy with >95% BTK occupancy maintained in 98% of patients before the next dose. Evobrutinib is currently under clinical investigation and is not approved for any use anywhere in the world.