Retigabine (ezogabine): in partial-onset seizures in adults with epilepsy

Retigabine (ezogabine in the US) opens neuronal voltage-gated potassium channels, resulting in resting membrane potential stabilization, neuronal subthreshold excitability control and anticonvulsant effects. The clinical efficacy of adjunctive oral retigabine in adults with inadequately controlled, partial-onset seizures was demonstrated in two large, well designed, phase III trials (RESTORE-1 and RESTORE-2), generally confirming the findings of an earlier phase IIb study. In the RESTORE trials, retigabine 600, 900 or 1200 mg/day was associated with significantly higher rates of response (i.e. reduction in 28-day total partial seizure frequency of ≥50%) than placebo during both the 12-week maintenance period and the entire 16- or 18-week double-blind phase (i.e. titration plus maintenance) of the studies. Retigabine recipients also had significantly greater median reductions from baseline in 28-day total partial seizure frequency than placebo recipients during these treatment periods. These benefits of retigabine were generally seen irrespective of age, gender, race and baseline seizure frequency, and were maintained for up to 12 months according to interim data from subsequent open-label extension studies, with some patients also experiencing seizure-free periods of up to 12 months. Retigabine was generally well tolerated in adults with partial-onset seizures in the RESTORE studies, with most adverse events being of mild or moderate severity.