The New Bar Set for Therapies in Treatment-Resistant Epilepsy: Jacqueline A. French, MD

WATCH TIME: 5 minutes

“We now have sort of set a new bar, and it’s going to be very hard for any other drug to be developed in the field that doesn’t really have a substantial improvement in seizures that’s demonstrable. We’re not going to go back to this can show a 40% median reduction compared to 20% in the placebo group.”

Treatment-resistant, or refractory, epilepsy has stood in the way of quality of life for patients and has proven to be a challenging obstacle for physicians in the field. Over the last 2 decades, 10 to 15 new therapies have come to the market to treat epilepsy but the number of individuals with refractory disease has been mostly maintained.

Although, just recently, some of the more novel therapies to make their way through the pipeline, particularly cenobamate (Xcopri; SK Life Science), which was approved in 2019. Recently, an analysis from the 2021 American Epilepsy Society (AES) Annual Meeting, December 3-7, in Chicago, Illinois, showed that treatment with cenobamate provided additional seizure freedom benefits for patients with uncontrolled focal seizures taking 1-3 antiseizure medications who were refractory to prior epilepsy-related surgery.¹

Recently, at the American Academy of Neurology (AAN) Annual Meeting, April 2-7, in Seattle, Washington, Jacqueline A. French, MD, professor, department of neurology, NYU Langone Health Center, and codirector, Epilepsy Clinical Trials, NYU Langone, Comprehensive Epilepsy Center, spoke with NeurologyLive® about another therapy that might help drive down that number, XEN1101. The investigational agent is a potent, selective KCNQ2/3 (Kv7.2/7.3) potassium channel positive allosteric opener being developed by Xenon Pharmaceuticals. French, who is also the founder/director of the Epilepsy Study Consortium, and chair of the phase 2 X-TOLE study (NCT03796962) steering committee, presented the data at AAN.^2,3

French also discussed her hopes for the future in drug development for treatment-resistant epilepsy that includes therapies that are disease-modifying rather than merely symptomatic, pointing to the reclassification of current agents to antiseizure medications from the older term, antiepileptic drugs, as a sign of that shift in thinking.

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REFERENCES
1. Abou-Khalil B, Aboumatar S, Klein P, Krauss GL, Sperling MR, Rosenfeld WE. Efficacy of cenobamate for uncontrolled focal seizures in patients with previous epilepsy-related surgery: post hoc analysis of a phase 3, multicenter, open-label study. Presented at: AES Annual Meeting; December 3-7, 2021; Chicago, IL, and virtual. Abstract 2.206
2. French JA, Porter R, Perucca E, et al. Phase 2b Efficacy and Safety of XEN1101, a Novel Potassium Channel Opener, in Adults with Focal Epilepsy (X-TOLE). Presented at: American Academy of Neurology Annual Meeting; April 2-7, 2022; Seattle, WA, and virtual. Abstract 000415.
3. Xenon Pharmaceuticals announces positives topline results from phase 2b ‘X-TOLE’ clinical trial of XEN1101 for the treatment of focal epilepsy. News release. Xenon Pharmaceuticals, Inc. October 4, 2021. Accessed October 5, 2021. https://www.globenewswire.com/news-release/2021/10/04/2307753/33485/en/Xenon-Pharmaceuticals-Announces-Positive-Topline-Results-from-Phase-2b-X-TOLE-Clinical-Trial-of-XEN1101-for-the-Treatment-of-Focal-Epilepsy.html