Challenges and Potential of BTK Inhibitors in MS Treatment: Bruce Cree, MD, PhD, MAS, FAAN

WATCH TIME: 5 minutes

"I do worry that the evobrutinib trial was a ‘canary in the coal mine’ and is going to tell us something. Unfortunately, it was disappointing for at least the relapsing studies with these other Bruton tyrosine kinase inhibitors."

Although there are several available high-efficacy therapies for patients living with multiple sclerosis (MS), many still experience significant disability worsening because of the limited effects of such drugs on central nervous system (CNS)-compartmentalized inflammation. Bruton tyrosine kinase (BTK) is an intracellular signaling molecule involved in regulation of maturation, survival, migration, and activation of B cells and microglia. Thus, BTK inhibitors may show promise for prevent disease progression better in MS by targeting immune cells on both sides of the blood-brain barrier.¹

In December 2023, evobrutinib (Merck KGaA/EMD Serono), an investigational BTK inhibitor in development for patients with MS, did not meet its primary end points of reducing relapse in the pivotal phase 3 EVOLUTION trials.² In both the evolutionRMS 1 (NCT04338022) and evolutionRMS 2 (NCT04338061) studies, evobrutinib failed to distinguish itself from oral teriflunomide (Aubagio; Sanofi) in the reduction of annualized relapse rate (ARR; evolutionRMS 1: 0.11 vs 0.11; evolutionRMS 2: 0.15 vs 0.14; P = NS in both trials). Notably, ARR values in the teriflunomide group were reportedly lower than previously seen in other phase 3 studies.

At the 2024 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held May 29 to June 1, in Nashville, Tennessee, Bruce Cree, MD, PhD, MAS, FAAN, will present a talk on future therapeutics in MS in a symposium surrounding hot topics in the field. Prior to the symposium, Cree, the clinical research director of the UCSF Multiple Sclerosis Center, sat down in an interview with NeurologyLive^® to discuss his reaction to the findings from evobrutinib’s clinical trial. He also talked about how BTK inhibitors compare with other classes of MS medications in terms of efficacy. In addition, Cree spoke about the new strategies being explored to treat MS, especially B cell depletion.

Click here for more coverage of CMSC 2024.

REFERENCES
1. Krämer J, Wiendl H. Bruton tyrosine kinase inhibitors in multiple sclerosis: evidence and expectations. Curr Opin Neurol. 2024;37(3):237-244. doi:10.1097/WCO.0000000000001269
2. Merck KGaA, Darmstadt, Germany provides update on phase 3 results for evobrutinib in relapsing multiple sclerosis. News release. December 5, 2023. Accessed May 30, 2024. https://www.emdgroup.com/en/news/evobrutinib-phase-lll.html