Long-term cenobamate retention, efficacy, and safety: outcomes from Expanded Access Programme
Abstract
Aim of the study. To evaluate the long-term retention rate, efficacy, and tolerability of adjunctive cenobamate (CNB) in patients with drug-resistant epilepsy within the Polish Expanded Access Programme (EAP).
Clinical rationale for the study. Long-term retention rate is a useful measure of effectiveness including efficacy, safety, and tolerability of antiseizure medications.
Material and methods. We conducted a multicentre retrospective analysis of consecutive patients with focal epilepsy treated with CNB in the EAP between January 2020 and May 2023. All patients who completed the open-label extension phases of the YKP3089C013 and YKP3089C017 trials were offered the opportunity to continue CNB treatment within the EAP. We analysed cenobamate retention, seizure outcomes, and adverse events.
Results. 38 patients (18 females; 47.3%) continued CNB treatment within the Expanded Access Programme for 41 months. The mean baseline age of patients was 39.3 years (range: 18–57). All patients were on polytherapy, with the most commonly used antiseizure medications being valproate, levetiracetam, and carbamazepine. Adjunctive CNB treatment resulted in a reduced mean seizure frequency from 8.1 seizures (range: 4-20) per month to 3 seizures (range: 0–8) per month. At the final follow-up, the median CNB dose was 200 mg/day (range: 50–350). Among the patients, 24 (63.1%) achieved ≥ 50% seizure reduction, and eight (21%) remained seizure-free for at least 12 months. One in three patients experienced adverse events, which resolved in half of the subjects. The most frequent adverse events were dizziness, somnolence, and headache. The retention rate after completing the open-label extension phase was 100%.
Conclusions and clinical implications. Long-term effectiveness, including ≥ 50% seizure reduction and a 100% retention rate, was sustained over 41 months of CNB treatment within the Expanded Access Programme. No new safety issues were identified. These results provide support for the potential long-term clinical benefits of cenobamate.
Keywords: cenobamateretention rateefficacysafetyadverse events
References
- Beghi E. The Epidemiology of Epilepsy. Neuroepidemiology. 2020; 54(2): 185–191.
- Nowak A, Rysz A, Dziedzic T, et al. Predictors of Class I epilepsy surgery outcome in tumour-related chronic temporal lobe epilepsy in adults. Neurol Neurochir Pol. 2019; 53(6): 466–475.
- 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): 279–286.
- Wężyk K, Słowik A, Bosak M. Predictors of remission in patients with epilepsy. Neurol Neurochir Pol. 2020; 54(5): 434–439.
- Löscher W, Potschka H, Sisodiya SM, et al. Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options. Pharmacol Rev. 2020; 72(3): 606–638.
- Roberti R, De Caro C, Iannone LF, et al. Pharmacology of Cenobamate: Mechanism of Action, Pharmacokinetics, Drug-Drug Interactions and Tolerability. CNS Drugs. 2021; 35(6): 609–618.
- 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.
- 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–e2322.
- Lattanzi S, Trinka E, Zaccara G, et al. Third-Generation Antiseizure Medications for Adjunctive Treatment of Focal-Onset Seizures in Adults: A Systematic Review and Network Meta-analysis. Drugs. 2022; 82(2): 199–218.
- Privitera M, Richy FF, Schabert VF. Indirect treatment comparison of cenobamate to other ASMs for the treatment of uncontrolled focal seizures. Epilepsy Behav. 2022; 126: 108429.
- Klein P, Aboumatar S, Brandt C, et al. Long-Term Efficacy and Safety From an Open-Label Extension of Adjunctive Cenobamate in Patients With Uncontrolled Focal Seizures. Neurology. 2022 [Epub ahead of print]; 99(10): e989–e998.
- 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. Epilepsia. 2021; 62(9): 2142–2150.
- Peña-Ceballos J, Moloney PB, Munteanu T, et al. Adjunctive cenobamate in highly active and ultra-refractory focal epilepsy: A "real-world" retrospective study. Epilepsia. 2023; 64(5): 1225–1235.
- Villanueva V, Santos-Carrasco D, Cabezudo-García P, et al. Real-world safety and effectiveness of cenobamate in patients with focal onset seizures: Outcomes from an Expanded Access Program. Epilepsia Open. 2023; 8(3): 918–929.
