Use of cenobamate for the treatment of focal epilepsy: an Italian expert opinion paper

ABSTRACT

Introduction

Cenobamate is a new antiseizure medication (ASM) recently introduced in the USA for the treatment of adults with focal-onset seizures. In March 2021, the European Commission authorized its use for the adjunctive treatment of focal-onset seizures with or without secondary generalization (focal seizures with or without progression to bilateral tonic-clonic seizures, according to current ILAE terminology) in adults with epilepsy not adequately controlled despite the treatment with at least two ASMs.

Areas covered

This review summarizes the mechanism of action, efficacy, and safety of Cenobamate. The authors provide their expert opinions on the use of this drug.

Expert opinion

The aim of this paper is to report on the Italian preliminary experience with the use of cenobamate, focusing on treatment goals, optimal dosing and titration schedules, strategies to minimize adverse effects, and identification of suitable candidates for treatment. There was agreement that slow titration may improve tolerability, and that clinically significant benefit can be achieved in many patients at relatively low doses. A favorable response to relatively low doses of cenobamate could be an early predictor of ultimate responsiveness. Overall, cenobamate is a welcome new treatment for adults with focal seizures resistant to conventional ASMs.

KEYWORDS:

• Cenobamate
• epilepsy
• focal seizures
• drug resistance

Article highlights

• Despite the existence of over 30 anti-seizure medications (ASM), including 20 over the last 30 years, a third of patients with epilepsy remain refractory to treatment, with no disease-modifying or preventive therapies until very recently.

• Cenobamate is a novel antiseizure medication (ASM) commercially available in Europe and in the U.S. for the treatment of focal seizures in adults. The mechanisms responsible for its antiseizure activity include enhancement of the inactivated state of voltage-gated sodium channels with blockade of the persistent sodium current, and positive allosteric modulation of GABAA receptors at a non-benzodiazepine binding site.

• CNB treatment has been associated with seizure freedom rates which are considerably higher than those reported for other ASMs.

• Slow titration may improve tolerability, and that clinically significant benefit can be achieved in many patients at relatively low doses.

• Concomitant ASM dose reductions is associated with more patients remaining on cenobamate.

• Based on available data, CNB appears to be a welcome addition to the pharmacological armamentarium for the treatment of patients with uncontrolled focal seizures.

Declaration of interest

C. Di Bonaventura has received speaker’s or consultancy honoraria from Angelini, Bial, Eisai, GW Pharma, Lusofarmaco and UCB Pharma. G. Di Gennaro has received speaker’s or consultancy fees from Angelini, Arvelle, Bial, GW, Eisai, Livanova, Lusofarmaco, UCB-Pharma. C.A. Galimberti has received speaker’s or consultancy fees from Angelini, Eisai, Sanofi, Lusofarmaco, Zogenix. A. La Neve has received speaker’s or consultancy fees from Eisai, GW, Mylan, Bial, Sanofi, Neuraxpharm, Arveille, Angelini and UCB Pharma. O. Mecarelli has received speaker’s or consultancy fees from Angelini, Bial, Eisai, GW Pharma, Lusofarmaco, Sanofi and UCB Pharma. E. Perucca has received speaker’s or consultancy fees from Angelini, Arvelle, Biogen, Biopas, Eisai, GW Pharma, Sanofi, PMI LifeSciences, SK Life Science, Sun Pharma, Takeda, UCB Pharma, Xenon Pharma and Zogenix. N. Pietrafusa has received speaker’s or consultancy fees from Zogenix and Angelini. N. Specchio has served on scientific advisory boards for GW Pharma, BioMarin, Arvelle, Marinus and Takeda; has received speaker honoraria from Eisai, Biomarin, Livanova, Sanofi; has served as an investigator for Zogenix, Marinus, Biomarin, UCB, Roche. F. Vigevano has received speaker’s or consultancy fees from Zogenix, Neurax Pharma, Angelini, Eisai, Neuraxpharm. F. Villani has received speaker’s or consultancy fees from Angelini, Eisai, UCB Pharma, Bial.

Reviewer disclosures

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

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14737175.2023.2171291

Additional information

Funding

The organization of the expert meeting and the preparation of this manuscript were supported by an unconditional grant from Angelini Pharma.