Perampanel monotherapy for the treatment of epilepsy: Clinical trial and real-world evidence.

Perampanel, a selective, non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, is a once-daily oral anti-seizure medication (ASM) for focal-onset seizures (FOS) and generalized tonic-clonic seizures (GTCS). In the US, perampanel is approved for the treatment of FOS (adjunctive and monotherapy), with or without focal to bilateral tonic-clonic seizures (FBTCS), in patients aged ≥4 years, and as adjunctive treatment of GTCS in patients aged ≥12 years. The monotherapy approvals in the US were based on the Food and Drug Administration's (FDA's) policy allowing extrapolation of adjunctive data to the monotherapy setting in the absence of randomized controlled monotherapy trials; since then, perampanel monotherapy has received approvals in approximately 48 countries. As there are key differences in clinical evidence of perampanel as adjunctive therapy vs monotherapy, we review the clinical outcomes of perampanel when administered as primary or secondary monotherapy. Eight publications reporting the efficacy and safety outcomes of perampanel monotherapy in clinical trial and real-world settings were selected during our literature search and are included; these comprise three Eisai-sponsored studies in patients with epilepsy: one prospective, open-label, Phase III clinical trial of patients with newly diagnosed epilepsy (Study 342 [FREEDOM]) and two retrospective, real-world Phase IV studies of patients with epilepsy who received perampanel during routine clinical care (Studies 504 and 506 [PROVE]); and five retrospective, real-world studies in patients with epilepsy who were prescribed perampanel during routine clinical care. Results from these studies demonstrated that seizure freedom may be achieved following treatment with perampanel monotherapy (either primary or secondary), with favorable retention rates and safety profiles. Overall, the clinical evidence supports the use of perampanel monotherapy both in newly diagnosed patients and in those who have been unable to control their seizures with other ASMs.