A post hoc analysis of the long‐term safety and efficacy of perampanel in Asian patients with epilepsy

Abstract

Summary This post hoc analysis assessed the long‐term safety, tolerability, and efficacy of perampanel in Asian patients with refractory focal seizures; an additional analysis assessed the effect of perampanel on focal impaired awareness seizures (FIAS) with focal to bilateral tonic‐clonic (FBTC) seizures. In this subanalysis, data from Asian patients ≥12 years of age who had focal seizures with FBTC seizures despite taking one to 3 concomitant antiepileptic drugs at baseline, and who had entered either the long‐term extension phase of 3 phase‐3 perampanel trials (study 307) or the 10‐week extension phase of study 335, were analyzed for the effect of perampanel on duration of exposure, safety, and seizure outcomes. Of 874 Asian patients included in the analysis, 205 had previously received placebo during the double‐blind phase‐3 trials and 669 had previously received perampanel 2‐12 mg/day; 313 had FIAS with FBTC seizures at core study baseline. The median duration of exposure to perampanel was 385.0 days, and the retention rate at one year was 62.6%. Overall, during the first 52 weeks of perampanel treatment, 777 patients (88.9%) had treatment‐emergent adverse events (TEAEs), most of which were mild to moderate in severity. The most frequent TEAEs were dizziness (47.1%), somnolence (22.3%), and nasopharyngitis (17.4%). During the first 52 weeks of perampanel treatment, median percent change in seizure frequency per 28 days from pre‐perampanel baseline for all focal seizures was −28.1%, and −51.7% for FIAS with FBTC seizures. The 50% responder rate relative to pre‐perampanel baseline for all focal seizures was 33.8%, and 51.1% for FIAS with FBTC seizures. Long‐term treatment with perampanel in Asian patients had safety, tolerability, and efficacy similar to that of the global population in the phase‐3 trials and extension study 307. The safety profile and response rate suggest benefit for an Asian population of patients with refractory epilepsy.

Utility and Safety of Perampanel in Pediatric FIRES and Other Drug-Resistant Epilepsies

“…This may be contributed by the differing developmental stages of the child, as well as various pharmacokinetics factors. 1 , 2 , 18 , 19 , 31 …”

“…This may be contributed by the differing developmental stages of the child, as well as various pharmacokinetics factors. 1,2,18,19,31 Limitations This is a retrospective and observational study. The number of patients reported in this study was small and the patient population was heterogeneous.…”

“…Perampanel is a novel antiepileptic drug (AED) and a noncompetitive antagonist of the ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor on postsynaptic neurons. 1 - 3 AMPA receptor blockade inhibits excitatory discharges and seizure propagation. 2 , 3 It is efficacious and safe in drug-resistant epilepsy and has a long half-life, of approximately 105 h. 1 - 3 Perampanel has efficacy in focal-onset seizures with or without secondarily-generalized seizures in phase III studies, has established safety and tolerability profile at doses up to 12 mg/day, and is approved by the US Food and Drug Administration (FDA) in the adjunctive treatment of focal-onset seizures with or without secondarily-generalized seizures for patients aged four or older.…”

“…[1][2][3] AMPA receptor blockade inhibits excitatory discharges and seizure propagation. 2,3 It is efficacious and safe in drug-resistant epilepsy and has a long half-life, of approximately 105 h. [1][2][3] Perampanel has efficacy in focal-onset seizures with or without secondarily-generalized seizures in phase III studies, has established safety and tolerability profile at doses up to 12 mg/day, and is approved by the US Food and Drug Administration (FDA) in the adjunctive treatment of focal-onset seizures with or without secondarilygeneralized seizures for patients aged four or older. [4][5][6][7][8] Febrile infection-related epilepsy syndrome (FIRES) is a rare catastrophic epilepsy syndrome of unknown etiology in previously healthy children.…”

Epilepsy in Asia

“…In the following 3 articles, the data for perampanel use in Asian patients enrolled in phase 3 clinical trials are reported. Tsai et al assess the efficacy, safety, and tolerability of perampanel as adjunctive therapy in Asian patients with focal epilepsy with or without secondary generalization; Nishida et al examine its efficacy and safety in Asian patients with primary or secondarily generalized tonic–clonic seizures; and Inoue et al investigate the long‐term use of perampanel in Asian patients with refractory focal seizures or complex partial seizures with or without secondary generalization. The 3 studies each found that the efficacy, safety, and tolerability of perampanel in Asian patients were similar to the results for the non‐Asian patients in phase 3 trials, suggesting a benefit also for this patient population.…”