The Evolving Landscape of Treatments for Multiple Sclerosis in 2024: Enrique Alvarez, MD, PhD

WATCH TIME: 6 minutes

“We really started to notice questions around emphasizing maybe some of the safety issues and trying to [understand] the sequencing of treatment. We've had a lot of discussion around de-escalation approaches versus high efficacy therapy early type approach to initiating treatment. Those treatment debates seem to keep going stronger and stronger towards just starting high efficacy therapies early. We're starting to see those therapies used much more heavily earlier in the disease course.”

As the landscape of care evolves in multiple sclerosis (MS), clinicians continue their efforts in optimizing therapeutic approaches for patients. Investigating de-escalation of therapies, which involves transitioning patients from high or moderate efficacy disease-modifying therapies to lower efficacy ones to lower risk of adverse effects, has been a topic of interest.¹ Along with recent developments in therapeutics, Bruton tyrosine kinase (BTK) inhibitors are another type of investigational treatment that shows promise in slowing disease progression. These inhibitors are cytoplasmic tyrosine kinase expressed by B cells and myeloid cells that target immune cells on both sides of the blood–brain barrier.²

In December 2023, it was announced that evobrutinib (Merck KGaA/EMD Serono), an investigational BTK inhibitor in development for patients with MS, did not meet its primary end point of reducing relapse in the phase 3 EVOLUTION trials.³ CD40L inhibitors like frexalimab (Sanofi) have also shown promise as well. In a phase 2 trial (NCT04879628), frexalimab showed a pronounced reduction of new gadolinium-enhancing lesions by 3 months in patients with relapsing multiple sclerosis MS.⁴

Enrique Alvarez, MD, PhD, associate professor of neurology, University of Colorado School of Medicine, sat down in an interview with NeurologyLive® to talk about how the surprising findings from evobrutinib trials might shape the landscape of MS treatment criteria. In the context of MS, he talked about the challenges and considerations surrounding the transition from high efficacy therapies to de-escalation approaches. In addition, Alvarez spoke about the insights that are anticipated from the ongoing phase 3 trials of anti-CD-40 monoclonal antibodies like frexalimab.

REFERENCES
1. Vollmer BL, Wolf AB, Sillau S, Corboy JR, Alvarez E. Evolution of Disease Modifying Therapy Benefits and Risks: An Argument for De-escalation as a Treatment Paradigm for Patients With Multiple Sclerosis. Front Neurol. 2022;12:799138. Published 2022 Jan 25. doi:10.3389/fneur.2021.799138
2. Krämer J, Bar-Or A, Turner TJ, Wiendl H. Bruton tyrosine kinase inhibitors for multiple sclerosis. Nat Rev Neurol. 2023;19(5):289-304. doi:10.1038/s41582-023-00800-7
3. Merck KGaA, Darmstadt, Germany provides update on phase 3 results for evobrutinib in relapsing multiple sclerosis. News release. December 5, 2023. Accessed February 13, 2024. https://www.emdgroup.com/en/news/evobrutinib-phase-lll.html
4. Positive phase 2 data of novel investigational anti-CD40L antibody frexalimab show significantly reduced disease activity in relapsing multiple sclerosis. News release. Sanofi. May 31, 2023. Accessed February 13, 2024. https://www.sanofi.com/en/media-room/press-releases/2023/2023-05-31-05-00-00-2678991