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Cenobamate in focal seizures: a profile of its use

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Abstract

Cenobamate (XCOPRI®), a novel tetrazole alkyl carbamate derivative, is approved in the USA for use as monotherapy and adjunctive therapy in adults with focal seizures (also known as partial-onset seizures). Its use (within the recommended dosage of ≤ 400 mg/day) significantly reduced focal seizure frequency relative to the use of placebo in short-term (≤ 18 weeks) multinational, phase 2 studies in adults with focal seizures, with antiepileptic benefits appearing to be sustained over the longer-term (30 months). Cenobamate appears to have low abuse potential and to be generally well tolerated over the short- and longer-term (up to 79 months), with most treatment-emergent adverse events (TEAEs) being mild or moderate in severity. The most frequently reported TEAEs (somnolence, dizziness and fatigue) were CNS related, dose dependent and similar to those seen with other anti-seizure medications.

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References

  1. Chen Z, Brodie MJ, Liew D, et al. Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study. JAMA Neurol. 2018;75(3):279–86.

    Article  PubMed  Google Scholar 

  2. XCOPRI® (cenobamate tablets), for oral use, CV: US prescribing information. Paramus: SK Life Science, Inc.; 2020.

  3. Krauss GL, Klein P, Brandt C, 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(1):38–48.

    Article  CAS  PubMed  Google Scholar 

  4. Nakamura M, Cho JH, Shin H, et al. Effects of cenobamate (YKP3089), a newly developed anti-epileptic drug, on voltage-gated sodium channels in rat hippocampal CA3 neurons. Eur J Pharmacol. 2019;855:175–82.

    Article  CAS  PubMed  Google Scholar 

  5. Sharma R, Nakamura M, Neupane C, et al. Positive allosteric modulation of GABAA receptors by a novel antiepileptic drug cenobamate. Eur J Pharmacol. 2020:173117.

  6. Kasteleijn-Nolst Trenite DGA, DiVentura BD, Pollard JR, et al. Suppression of the photoparoxysmal response in photosensitive epilepsy with cenobamate (YKP3089). Neurology. 2019;93(6):e559–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Vernillet L, Greene SA, Kamin M. Pharmacokinetics of cenobamate: results from single and multiple oral ascending-dose studies in healthy subjects. Clin Pharmacol Drug Dev. 2020;9(4):428–43.

    Article  CAS  PubMed  Google Scholar 

  8. Vernillet L, Greene SA, Kim HW, et al. Mass balance, metabolism, and excretion of cenobamate, a new antiepileptic drug, after a single oral administration in healthy male subjects. Eur J Drug Metab Pharmacokinet. 2020. https://doi.org/10.1007/s13318-020-00615-7.

    Article  PubMed  Google Scholar 

  9. Kim H, Hwang J, Yoon D, et al. Safety, tolerability and pharmacokinetics of cenobamate (YKP3089) following single ascending doses in healthy Japanese subjects [abstract no. PIII-085]. In: American Society for Clinical Pharmacology and Therapeutics Annual Meeting. 2020.

  10. Chung SS, French JA, Kowalski J, et al. Randomized phase 2 study of adjunctive cenobamate in patients with uncontrolled focal seizures. Neurology. 2020;94(22):e2311–22.

    Article  CAS  PubMed  Google Scholar 

  11. Klein P, Krauss GL, Aboumatar S. Long-term efficacy and safety of adjunctive cenobamate in patients with uncontrolled focal seizures: open-label extension of a randomized clinical study [abstract no. 2.206]. In: 73rd Annual Meeting of the American Epilepsy Society. 2019.

  12. French JA, Chung SS, Krauss GL, et al. Long-term safety of adjunctive cenobamate in patients with uncontrolled focal seizures: open-label extension of a randomized clinical study [abstract no. 3.297]. In: 73rd Annual Meeting of the American Epilepsy Society. 2019.

  13. Kamin M, Ferrari L. Time to onset of efficacy in seizure reduction with cenobamate (YKP3089) in patients with uncontrolled partial seizures from 2 randomized clinical trials [abstract no. P1.5-032]. Neurology. 2019;92(15 Suppl).

  14. Rosenfeld WE, Ferrari L, Nisman A. Efficacy of adjunctive cenobamate in patients with uncontrolled focal seizures based on number of concomitant antiepileptic drugs, seizure frequency, and epilepsy duration at baseline [abstract no. 1.295]. In: 73rd Annual Meeting of the American Epilepsy Society. 2019.

  15. US FDA Center for Drug Evaluation and Research. Summary review. 2019. https://www.fda.gov. Accessed 17 June 2020.

  16. Ferrari L, Rosenfeld WE, Kamin M. Cenobamate adverse events by time of onset and dose from two randomized clinical studies in patients with uncontrolled focal seizures [abstract no. 1.322]. In: 73rd Annual Meeting of the American Epilepsy Society. 2019.

  17. Kamin M, Rosenfeld WE, Ferrari L. Safety of cenobamate for the treatment of focal seizures, following 1-week vs. 2-week titration schedules [abstract no. 3.295]. In: 73rd Annual Meeting of the American Epilepsy Society. 2019.

  18. Sperling MR, Klein P, Aboumatar S, et al. Cenobamate (YKP3089) as adjunctive treatment for uncontrolled focal seizures in a large, phase 3, multicenter, open-label safety study. Epilepsia. 2020. https://doi.org/10.1111/epi.16525.

    Article  PubMed  PubMed Central  Google Scholar 

  19. American College of Clinical Pharmacy. PSAP pharmacotherapy self-assessment program: epilepsy. Kansas City: ACCP; 2018.

    Google Scholar 

  20. Thijs RD, Surges R, O'Brien TJ, et al. Epilepsy in adults. Lancet. 2019;393(10172):689–701.

    Article  PubMed  Google Scholar 

  21. Kanner AM, Ashman E, Gloss D, et al. Practice guideline update summary. Efficacy and tolerability of the new antiepileptic drugs I: treatment of new-onset epilepsy. Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2018;91(2):74–81.

    Article  CAS  PubMed  Google Scholar 

  22. Kanner AM, Ashman E, Gloss D, et al. Practice guideline update summary. Efficacy and tolerability of the new antiepileptic drugs II: treatment-resistant epilepsy. Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2018;91(2):82–90.

    Article  CAS  PubMed  Google Scholar 

  23. Allers K, Essue BM, Hackett ML, et al. The economic impact of epilepsy: a systematic review. BMC Neurol. 2015;15:245.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Leinwand B, Hughes KE. A budget impact analysis of cenobamate for the treatment of refractory partial-onset epilepsy [abstract no. PND28]. Value Health. 2019;22(Suppl 2):S274–5.

    Article  Google Scholar 

  25. Keam SJ. Cenobamate: first approval. Drugs. 2020;80(1):73–8.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The article was updated from Drugs 2020;80:73–78 [25], and was reviewed by: C. Brandt, Bethel Epilepsy Centre, Mara Hospital, Bielefeld, Germany; H. Steve White, School of Pharmacy, University of Washington, Seattle, WA, USA. During the peer review process, SK Life Science Inc., the marketing authorization holder of cenobamate, was also offered an opportunity to provide a scientific accuracy review of their data. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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    Sheridan M. Hoy

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Correspondence to Sheridan M. Hoy.

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The preparation of this review was not supported by any external funding.

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Sheridan M. Hoy is an employee of Adis International Ltd./Springer Nature, is responsible for the article content and declares no conflicts of interest.

Additional information

Enhanced material for this Adis Drug Q&A can be found at https://doi.org/10.6084/m9.figshare.12580346.

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Hoy, S.M. Cenobamate in focal seizures: a profile of its use. Drugs Ther Perspect 36, 327–334 (2020). https://doi.org/10.1007/s40267-020-00754-6

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  • DOI: https://doi.org/10.1007/s40267-020-00754-6

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