Evobrutinib Reduces Relapse Rate, Lesion Load, and Neurofilament Light Levels
Post-hoc analysis of data from a trial (NCT02975349) of evobrutinib (EMD Serono, Rockland, MA) for relapsing forms of multiple sclerosis (MS) showed reduced levels of neurofilament light (NfL), a biomarker of axon degeneration. Participants in the trial who had an NfL level measured at baseline and at least once after treatment began (n=166). The largest relative reductions of NfL levels vs placebo were observed at weeks 12 and 24 in individuals who had 75 mg evobrutinib twice daily.
These results, combined with previous clinical trial data that demonstrated a reduction in T1 Gd+ lesion and annual relapse reduction (ARR), further support the hypothesis that evobrutinib may affect progressive neurodegenerative aspects of MS within the central nervous system (CNS). A phase 3 clinical trial (NCT04338061) of evobrutinib for MS is ongoing.
“Blood NfL is a biomarker that may allow monitoring of disease activity and treatment response, which could be less burdensome and more sensitive than other standard clinical measures for MS patients,” said Jens Kuhle, MD, PhD, head, Multiple Sclerosis Centre, University Hospital, Basel. “These data provide key insights into the role evobrutinib may play in modulating the clinical course of MS and further suggest that BTK inhibition with evobrutinib may reduce tissue damage associated with MS.”
Evobrutinib is an investigational Bruton tyrosine kinase (BTK) inhibitor thought to inhibit primary B-cell responses such as proliferation and antibody and cytokine release without directly affecting T cells. In pharmacokinetic studies, phosphorylated BTK (pBTK) levels were highly expressed in subsets of B cells isolated treated participants. In vitro, evobrutinib decreased CXCR3+ memory B cell transmigration through human CNS endothelial cell monolayers, suggesting that the therapy may affect activity of pathogenic B cells and modulate the progressive course of MS.
These data were presented at the virtual 2021 American Academy of Neurology (AAN) Virtual Annual Meeting April 17-22, 2021.