Evobrutinib, BTK Inhibitors, and the Associations With Neurofilament Light: Jens Kuhle, MD, PhD

WATCH TIME: 3 minutes

"The good thing is the straightforward specificity of neurofilament light. It’s neuron-specific and completely unspecific to the mechanisms leading to their destruction. But this unspecified part can also be a benefit in some situations where you want to quantify neuronal degeneration."

The investigational agents called Bruton tyrosine kinase (BTK) inhibitors have begun to make headway in the multiple sclerosis treatment pipeline, with several currently in phase 2 studies. In a recent analysis, EMD Serono’s evobrutinib significantly lowered blood neurofilament light chain (NfL), a biomarker of neuro-axonal damage, in a 24-week randomized study. The analysis, presented at the 2022 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, June 1-4, in National Harbor, Maryland, evaluated the differences of evobrutinib 75 mg once daily or 75 mg twice daily against placebo/low dose evobrutinib, with NfL levels stratified as either high (≥11.36 pg/mL) or low (<11.36 pg/mL).

In a cohort of 162 patients with relapsing MS, the odds of qualified relapse were significantly reduced for the high-dose group vs placebo/low dose when stratified by baseline NfL levels (odds ratio, 0.12; P = .0028). Led by Jens Kuhle, MD, PhD, this was the first study describing the interaction of blood NfL levels and the effects of BTK inhibition in patients with MS. To learn more about the current role of BTK inhibitors, as well as the overall thoughts on evobrutinib’s association with NfL levels, NeurologyLive® sat down with Kuhle. The head of the MS center and senior physician at University Hospital Basel provided commentary on the recent uptake in NfL-related research, as well as the questions still surrounding these new medications.

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REFERENCES
1. Montalban X, Wolinsky JS, Arnold DL, et al. Safety and efficacy of evobrutinib, a Bruton Tyrosine kinase inhibitor, in relapsing multiple sclerosis over 2.5 years of the open-label extension to a phase 2 trial. Presented at: 2022 CMSC Annual Meeting; June 1-4; National Harbor, Maryland. Abstract DMT02.