Perampanel Monotherapy for the Treatment of Epilepsy: Evidence From a Clinical Trial (Study 342) and Real-World Use (Studies 504 and 506)

초록

Purpose: In the US and Japan, perampanel is approved for focal-onset seizures (FOS; adjunctive/monotherapy) in patients aged ≥4 years and generalised tonic-clonic seizures (adjunctive) in patients aged ≥12 years. This analysis assessed efficacy/safety of perampanel monotherapy in patients with epilepsy using data from clinical and real-world studies. Method: Patients with epilepsy were included in Studies 504 (if prescribed perampanel monotherapy) and 506 (if initiating perampanel after 1 January 2014); patients received perampanel as primary/secondary monotherapy. Study 342 recruited untreated patients aged 12–74 years with FOS, with/without focal to bilateral tonic-clonic seizures (FBTCS); patients received perampanel 4 mg/day (maximum: 8 mg/day). Endpoints: retention rate (Studies 504/506, primary); seizure-freedom rate (Study 342, primary; Studies 504/506, secondary); treatment-emergent adverse events (TEAEs). Result: In Study 504, 60 patients received perampanel monotherapy. Retention rates were 55.6% (n = 15/27; 12 months) and 60.0% (n = 3/5; 24 months). Mean (standard deviation [SD]) maximum dose: 7.3 (2.8) mg/day. Seizure-freedom rate for ≥3 months was 55.0% (n = 22/40). In Study 506, 47 patients received perampanel monotherapy. Retention rates were 48.7% (n = 19/39; 12 months) and 45.5% (n = 10/22; 24 months). Mean (SD) maximum dose: 7.2 (2.7) mg/day. Seizure-freedom rate was 100.0% (n = 2/2) at Months 22–24. Most patients in Studies 504 and 506 had refractory epilepsy. In Study 342, 89 patients received ≥1 perampanel dose. Mean (SD) maximum dose: 4.9 (1.7) mg/day. Most patients with ≥1 post-dose efficacy measurement in the 4-mg Maintenance Period (n = 73) achieved seizure freedom (4 mg/day: 63.0%; 4 or 8 mg/day: 74.0%). TEAEs occurred in 22/60 (36.7%; Study 504) and 17/47 (36.2%; Study 506) patients, and 57/89 (64.0%; 4 mg/day) and 67/89 (75.3%; 4 and/or 8 mg/day) patients in Study 342; most common was dizziness. Conclusions: These data support perampanel monotherapy as treatment for FOS, with/without FBTCS, and refractory epilepsy. Funding: Eisai Inc., Eisai Co., Ltd., and Eisai Ltd.