Cenobamate for the treatment of focal epilepsies

ABSTRACT

Introduction

Antiseizure drugs (ASDs) play a central and crucial role in the treatment of epilepsy patients because the majority require anticonvulsant treatment for an extended period of time. Due to the fact that 30% of patients are refractory to medical treatment, new therapeutic options are necessary. Cenobamate is the latest approved antiepileptic drug in focal epilepsy, and its mode of action is thought to be mediated by blocking voltage-gated sodium channels and interaction with the GABAergic system.

Areas covered

This article reviews animal studies, pharmacokinetics, pharmacodynamics, and the phase 1 to 3 trials and open-label extension data on cenobamate.

Expert opinion

Cenobamate has the potential to perform as an important ASD because trial data are indicative of remarkable responder and seizure freedom rates so far not seen with other ASDs. Cenobamate demonstrated significant efficacy at a dosage between 100 and 400 mg per day. The side-effect profile of this drug is comparable to other ASDs and is mainly CNS related; in particular, somnolence, dizziness, headache, diplopia, and nystagmus. However, slow titration is mandatory to decrease the risk of drug rash with eosinophilia and systemic symptoms (DRESS) that was observed in several patients with fast uptitration schemes.

KEYWORDS:

• Cenobamate
• YKP3089; epilepsy
• seizure; anticonvulsant; antiepileptic drug

Article highlights

• Cenobamate was approved end of 2019 (FDA) for the treatment of partial-onset seizures in adult patients.

• Mode of action is thought to be mediated by blocking voltage-gated sodium channels and interaction with the GABAergic system.

• Data from randomized-controlled trials show remarkable responder and seizure freedom rates.

• The main adverse events are somnolence, dizziness, headache, diplopia, and nystagmus.

• Slow titration is mandatory to decrease the risk of drug rash with eosinophilia and systemic symptoms (DRESS).

Box 1. Drug summary box

Table

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Declaration of interest

A Strzelczyk reports receiving personal fees and grants from Arvelle Therapeutics, Desitin Arzneimittel, Eisai, GW Pharmaceuticals, LivaNova, Marinus Pharmaceuticals, Medtronic, Sage Therapeutics, UCB Pharma, and Zogenix. F Rosenow reports receiving personal fees from Arvelle Therapeutics, Desitin, Eisai, GW Pharmaceuticals, Medtronic, Novartis, UCB Pharma and Shire as well as grants from the European Union, the German Ministry for Education and Research, the State of Hessen, the Deutsche Forschungsgemeinschaft, and the Detlev-Wroble-Fonds for Epilepsy. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors are supported by the State of Hessen by a LOEWE grant for their Center for Personalized and Translational Epilepsy Research.