Rationale: LGS is a severe refractory childhood-onset epilepsy characterized by a triad of multiple seizure types (including drop seizures), intellectual disability, and certain electroencephalographic abnormalities. Study 338 (NCT02834793) evaluated the long-term efficacy and safety of adjunctive perampanel in patients with uncontrolled seizures with LGS. We report a post hoc analysis by treatment period to assess early and sustained treatment effect.
Methods: Study 338 enrolled patients with LGS who were receiving 1–4 concomitant anti-seizure medications and had an average of ≥ 2 drop seizures/week during baseline. The study consisted of a randomized, double-blind, placebo-controlled Core Study (6-week Titration, 12-week Maintenance) and Extension Phase (6-week Conversion, 46-week Maintenance). During the Conversion Period, perampanel-treated patients continued to receive perampanel (prior perampanel group) and previously placebo-treated patients began perampanel treatment (prior placebo group). Primary endpoint: median percent change from baseline in drop seizure frequency/28 days during the Core Study Titration and Maintenance Periods. Secondary endpoints: median percent change from baseline in non-drop and all-seizure frequency/28 days, responder rates (50%, 75%, and seizure-freedom), and safety outcomes. Outcomes were assessed in the prior perampanel vs prior placebo groups during Titration (6-week Core Study Titration vs 6-week Extension Phase Conversion [i.e. when placebo-treated patients began perampanel treatment]), Maintenance (12-week Core Study Maintenance vs initial 12 weeks of Extension Phase Maintenance), and Long-term Treatment (entire 52-week Extension Phase vs remaining 34 weeks of Extension Phase Maintenance) Periods._x000D_
Results: In the Extension Phase, 58 patients received perampanel (prior perampanel group, n=26; prior placebo group, n=32). Reductions in seizure frequency/28 days were achieved in the Titration Period and maintained in the Maintenance and Long-term Treatment Periods, irrespective of prior treatment (Table 1). Responder rates were generally maintained through all the treatment periods. Incidences of treatment-emergent adverse events (TEAEs) remained generally comparable throughout the study; treatment-related TEAEs and TEAEs leading to dose reduction declined following the Titration Period (Table 2). Two deaths (deemed unrelated to perampanel treatment) occurred during the Long-term Treatment Period. Most common TEAEs during each of the treatment periods were: somnolence (12.1%; Titration), upper respiratory tract infection (9.3%; Maintenance), and nasopharyngitis and pyrexia (each event, 9.8%; Long-term Treatment).
Conclusions: Adjunctive perampanel demonstrated early-onset efficacy that was sustained long-term (at least 46 weeks), showed efficacy in previously placebo-treated patients, and was well tolerated in patients with LGS, regardless of treatment period._x000D_
Funding: Eisai Co., Ltd., Eisai Inc., and Eisai Ltd.