Development of lacosamide for the treatment of partial-onset seizures

Pamela Doty, David Hebert, Francois-Xavier Mathy, William Byrnes, James Zackheim, Kelly Simontacchi, Pamela Doty, David Hebert, Francois-Xavier Mathy, William Byrnes, James Zackheim, Kelly Simontacchi

Abstract

Lacosamide is an antiepileptic drug (AED) available in multiple formulations that was first approved in 2008 as adjunctive therapy for partial-onset seizures (POS) in adults. Unlike traditional sodium channel blockers affecting fast inactivation, lacosamide selectively enhances sodium channel slow inactivation. This mechanism of action results in stabilization of hyperexcitable neuronal membranes, inhibition of neuronal firing, and reduction in long-term channel availability without affecting physiological function. Lacosamide has a well-characterized and favorable pharmacokinetic profile, including a fast absorption rate, minimal or no interaction with cytochrome P-450 izoenzymes, and a low potential for drug-drug interactions. Lacosamide clinical development included three placebo-controlled, double-blind, randomized trials conducted in more than 1300 patients, each demonstrating safety and efficacy of lacosamide compared to placebo as adjunctive therapy for adults with POS. The clinical use of lacosamide may broaden, pending results of trials evaluating its use as monotherapy for POS in adults, as treatment for epilepsy in pediatric subjects, and as adjunctive treatment for uncontrolled primary generalized tonic-clonic seizures in those with idiopathic generalized epilepsy.

Keywords: antiepileptic drug; epilepsy; lacosamide; partial-onset seizures.

© 2013 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

Figures

Figure 1
Figure 1
Mechanism of action of lacosamide, classical anticonvulsants, and local anesthetics.
Figure 2
Figure 2
Design of the three lacosamide phase IIb/III studies.
Figure 3
Figure 3
Pooled analyses of lacosamide phase IIb/III clinical trials. Shown is the change in seizure frequency per 28 days (A) and the proportion of patients experiencing a ≥50% (B) or 75% (C) reduction in the seizure frequency following treatment with locosamide or placebo.

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