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Observational Study
. 2025 May;66(5):1519-1528.
doi: 10.1111/epi.18308. Epub 2025 Feb 11.

A multicenter cohort study on the efficacy, retention, and tolerability of cenobamate in patients with developmental and epileptic encephalopathies

Elisa Buhleier  1 , Susanne Schubert-Bast  1   2 , Susanne Knake  3 , Felix von Podewils  4 , Hajo M Hamer  5 , Nico Melzer  6 , Gerhard Kurlemann  7 , Kerstin Alexandra Klotz  8   9 , Laurent M Willems  1 , Felix Rosenow  1 , Andreas Brunklaus  10   11 , Adam Strzelczyk  1   10
Affiliations
Observational Study

A multicenter cohort study on the efficacy, retention, and tolerability of cenobamate in patients with developmental and epileptic encephalopathies

Elisa Buhleier et al. Epilepsia. 2025 May.

Abstract

Objective: This study was undertaken to evaluate retention and treatment characteristics of cenobamate (CNB) in patients with developmental and epileptic encephalopathies (DEEs) in clinical practice.

Methods: This multicenter, retrospective cohort study recruited all patients with DEEs who started CNB treatment between October 2020 and April 2023 at participating epilepsy centers.

Results: A total of 41 patients (mean age = 28.3 ± 13.1 years, median = 26 years, range = 4-73 years; 24 male [58.5%]) were treated with CNB. Of these, 33 had Lennox-Gastaut syndrome, seven had tuberous sclerosis complex, and one had Dravet syndrome. The median number of antiseizure medications (ASMs) at enrollment was three, and patients had a median of eight failed ASMs in the past. The retention rate for CNB was 94.9% at 3 months, 82.9% at 6 months, and 72.4% at 12 months of follow-up. Cumulative exposure to CNB was 477 months (39.2 years). Efficacy (50% responder rate) at 3 months was 39% including 7.3% seizure-free patients. Long-term, the 50% responder rate at 12 months was 34.5% (seizure-free [10.3%]). There was no difference in response at 3 months regarding sex, age (adult vs. children), previous and concomitant number of ASMs, or first target dose of CNB. Treatment-emergent adverse events were predominantly sedation and dizziness and were observed in 58.5% of patients. Children and adolescents showed comparable efficacy, retention, and tolerability compared to adults.

Significance: The findings from this open-label, retrospective study suggest that CNB may be effective in some patients with DEEs. Its overall use in DEEs seems to be safe and well tolerated. We observed similar response, retention, and adverse event profiles in children and adults.

Keywords: Dravet syndrome; Lennox–Gastaut syndrome; antiseizure medication; epilepsy; seizure.

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Conflict of interest statement

E.B. and L.M.W. do not report any conflicts of interest. S.S.‐B. has received personal fees and grants from Angelini Pharma, Biocodex, Desitin Arzneimittel, Eisai, Jazz Pharmaceuticals, Marinus, Takeda, and UCB Pharma. S.K. has received speaker's honoraria from Bial, Destin Arzneimittel, Eisai, Jazz Pharma, Merck Serono, and UCB. F.v.P. has received personal fees and grants from Angelini Pharma, Desitin Arzneimittel, Eisai, Jazz Pharmaceuticals, UCB Pharma, Nutricia Milupa, Neuraxpharm, and Bial. H.M.H. has served on the scientific advisory boards of Angelini, UniQure, Eisai, GW/Jazz, and UCB Pharma. He has served on the speakers' bureaus of or received unrestricted grants from Angelini, Ad‐Tech, Alnylam, Bracco, Desitin, Eisai, Jazz, LivaNova, Nihon Kohden, Pfizer, and UCB Pharma. N.M. has received honoraria for lecturing and travel expenses for attending meetings from Biogen Idec, GlaxoSmithKline, Teva, Novartis Pharma, Bayer Healthcare, Genzyme, Alexion Pharmaceuticals, Fresenius Medical Care, Diamed, UCB Pharma, Angelini Pharma, Bial, and Sanofi‐Aventis, has received royalties for consulting from UCB Pharma, Alexion Pharmaceuticals, and Sanofi‐Aventis, and has received financial research support from Euroimmun, Fresenius Medical Care, Diamed, Alexion Pharmaceuticals, and Novartis Pharma. G.K. has received speaker's honoraria from Angelini Pharma, Desitin Arzneimittel, Eisai, Jazz Pharmaceuticals, Takeda, UCB Pharma, Neuraxpharm, Stada Arzneimittel, Precisis, and Alexion Pharmaceuticals. K.A.K. has received speaker's honoraria from Biocodex, Desitin Arzneimittel, Eisai, Jazz Pharmaceuticals, and UCB Pharma. F.R. has received personal fees from Angelini Pharma, Desitin Arzneimittel, Eisai, Jazz Pharmaceuticals, Roche Pharma, Stoke Therapeutics, and UCB Pharma and grants from the Detlev‐Wrobel‐Fonds for Epilepsy Research, the Deutsche Forschungsgemeinschaft, the Federal Ministry of Education and Research, the LOEWE Program of the State of Hesse, and the European Union. A.B. has received honoraria for presenting at educational events, serving on advisory boards, and consultancy work for Biocodex, Encoded Therapeutics, Jazz/GW Pharma, Servier, Stoke Therapeutics, and UCB/Zogenix. A.S. has received personal fees and grants from Angelini Pharma, Biocodex, Desitin Arzneimittel, Eisai, Jazz Pharmaceuticals, Longboard, Neuraxpharm, Takeda, UCB Pharma, and UNEEG Medical. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Figures

FIGURE 1
FIGURE 1
Responder rates over time for (A) total seizures and (B) generalized tonic–clonic seizures (GTCS).
FIGURE 2
FIGURE 2
(A) Percentage of patients according to seizure days per month across seven incremental categories at baseline and at the final follow‐up after initiation of cenobamate. (B) Physician‐assessed Clinical Global Impression of Change (CGI‐C).
FIGURE 3
FIGURE 3
Retention rate of cenobamate (A) in the complete cohort and (B) stratified for adults and children or adolescents (log‐rank p‐value = .623).
See this image and copyright information in PMC

References

    1. Schmitz B, Lattanzi S, Vonck K, Kälviäinen R, Nashef L, Ben‐Menachem E. Cenobamate in refractory epilepsy: overview of treatment options and practical considerations. Epilepsia Open. 2023;8:1241–1255. - PMC - PubMed
    1. Strzelczyk A, Mann C, Willems LM, Rosenow F, Bauer S. Cenobamate for the treatment of focal epilepsies. Expert Opin Pharmacother. 2020;21:2215–2223. - PubMed
    1. Brigo F, Lattanzi S. Cenobamate add‐on therapy for drug‐resistant focal epilepsy. Cochrane Database Syst Rev. 2024;8(8):CD014941. 10.1002/14651858.CD014941.pub2 - DOI - PMC - PubMed
    1. Krauss GL, Klein P, Brandt C, Lee SK, Milanov I, Milovanovic M, et al. Safety and efficacy of adjunctive cenobamate (YKP3089) in patients with uncontrolled focal seizures: a multicentre, double‐blind, randomised, placebo‐controlled, dose‐response trial. Lancet Neurol. 2020;19:38–48. - PubMed
    1. Sperling MR, Klein P, Aboumatar S, Gelfand M, Halford JJ, Krauss GL, et al. Cenobamate (YKP3089) as adjunctive treatment for uncontrolled focal seizures in a large, phase 3, multicenter, open‐label safety study. Epilepsia. 2020;61:1099–1108. - PMC - PubMed

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