Abstracts

Rationale:
In the US and Japan, perampanel is approved for partial-onset seizures (POS; adjunctive and monotherapy) in patients aged ≥ 4 years, and adjunctive treatment of primary generalized tonic-clonic seizures in patients aged ≥ 12 years. Perampanel is approved in 45 countries as monotherapy for POS with/without secondarily generalized seizures (SGS). We review clinical evidence for perampanel monotherapy from 2 multicenter, retrospective, non-interventional, Phase IV Studies (504 [NCT02736162; Europe, Russia] and 506 [NCT03208660; PROVE; US]), and an open-label, Phase III clinical trial (Study 342 [NCT03201900; FREEDOM]; Japan, South Korea).
Method:
Patients with a diagnosis of epilepsy were included in Studies 504 (if prescribed perampanel monotherapy) and 506 (if initiating perampanel after January 1, 2014); patients could receive perampanel as primary (in the absence of concomitant anti-seizure medications [ASMs]) or secondary (withdrawal of concomitant ASMs) monotherapy. Study 342 recruited previously untreated patients aged 12–74 years with POS, with/without SGS; patients received perampanel 4 mg/day, with titration up to 8 mg/day in case of seizure. Primary endpoints were retention rates up to 24 months (Studies 504 and 506) and seizure-freedom rate in the 4 mg/day 26-week Maintenance Period (Study 342). In Phase IV studies, seizure-freedom rate (for ≥ 3 months on perampanel monotherapy [Study 504] or at defined timepoints [Study 506]) was a secondary endpoint. Treatment-emergent adverse events (TEAEs) were monitored.
Results:
Primary endpoints are in Table 1. In Study 504, 60 patients received monotherapy (primary: n=9; secondary: n=51). Mean (standard deviation [SD]) cumulative duration of perampanel monotherapy exposure was 8.8 (8.2) months; mean (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 (primary: n=33; secondary: n=14). Mean (SD) cumulative duration of perampanel monotherapy exposure was 13.5 (11.8) months (for secondary monotherapy this includes time on adjunctive treatment); 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 Phase IV studies were diagnosed with epilepsy ≥ 5 years prior, suggesting refractory disease. In Study 342, 89 patients received ≥ 1 perampanel dose. Mean (SD) cumulative duration of perampanel monotherapy exposure was 41.0 (25.5) weeks; 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%). An overview of TEAEs across studies is shown in Table 2.
Conclusion:
Evidence from the Phase III clinical and Phase IV real-world studies support use of perampanel monotherapy in newly diagnosed patients with POS, with/without SGS, and those with refractory epilepsy who have been unable to control their seizures with other ASMs. Our data support perampanel as an early-line treatment option.
Funding:
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Funding:
: Eisai Inc., Eisai Co., Ltd., and Eisai Ltd.