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.