Article type: Narrative Review
Article title: Cenobamate (YKP3089) and Drug-Resistant Epilepsy: A Review of the Literature
Journal: Medicina
Year: 2023
Authors: Jamir Pitton Rissardo, Ana LetÃcia Fornari Caprara
E-mail: jamirrissardo@gmail.com
ABSTRACT
Cenobamate (CNB), ([(R)-1-(2-chlorophenyl)-2-(2H-tetrazol-2-yl)ethyl], is a novel tetrazole alkyl carbamate derivative. In November 2019, the Food and Drug Administration approved Xcopri®, marketed by SK Life Science Inc., (Paramus, NJ, USA) for adult focal seizures. The European Medicines Agency approved Ontozry® by Arvelle Therapeutics Netherlands B.V.(Amsterdam, The Neatherlands) in March 2021. Cenobamate is a medication that could potentially change the perspectives regarding the management and prognosis of refractory epilepsy. In this way, this study aims to review the literature on CNB’s pharmacological properties, pharmacokinetics, efficacy, and safety. CNB is a highly effective drug in managing focal onset seizures, with more than twenty percent of individuals with drug-resistant epilepsy achieving seizure freedom. This finding is remarkable in the antiseizure medication literature. The mechanism of action of CNB is still poorly understood, but it is associated with transient and persistent sodium currents and GABAergic neurotransmission. In animal studies, CNB showed sustained efficacy and potency in the 6 Hz test regardless of the stimulus intensity. CNB was revealed to be the most cost-effective drug among different third-generation antiseizure medications. Also, CNB could have neuroprotective effects. However, there are still concerns regarding its potential for abuse and suicidality risk, which future studies should clearly assess, after which protocols should be changed. The major drawback of CNB therapy is the slow and complex titration and maintenance phases preventing the wide use of this new agent in clinical practice.
Keywords: cenobamate; YKP3089; Xcopri; Ontozry; epilepsy; seizure; focal; generalized; drug resistant; antiseizure medication
Full text available at:
DOI
10.3390/medicina59081389
Citation
Rissardo JP, Fornari Caprara AL. Cenobamate (YKP3089) and Drug-Resistant Epilepsy: A Review of the Literature. Medicina 2023; 59:1389.
Figure 1. Chemical structure of some alkyl-carbamates with antiseizure activity. Carisbamate, cenobamate, felbamate, and retigabine (ezogabine). Note that felbamate is a dicarbamate. The other drugs are monocarbamates.
Figure 2. Physicochemical properties of cenobamate. The pink area represents the optimal range for each property. Abbreviation: LIPO: lipophilicity; FLEX: flexibility; INSAT: saturation; INSOL: solubility.
Figure 3. Clinical trials with cenobamate (YKP3089) registered in the ClinicalTrials.gov database.
Figure 4. Effects of cenobamate (CNB) on drug levels of antiseizure medications (ASMs). For ASMs whose metabolism can be increased by CNB, consider increasing the dose of the ASM. For ASMs whose metabolism can be decreased by CNB, consider reducing the dose of the ASM.