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. 2025 Oct 10:32:100833.
doi: 10.1016/j.ebr.2025.100833. eCollection 2025 Dec.

Long-term efficacy and safety of perampanel in patients aged 60 years and older with focal seizures: Post hoc analysis of phase III open-label extension studies stratified by enzyme-inducing anti-seizure medication use

Rohit Marawar  1 , Ilo E Leppik  2 , Robert T Wechsler  3 , Anna Patten  4 , Leock Y Ngo  5
Affiliations

Long-term efficacy and safety of perampanel in patients aged 60 years and older with focal seizures: Post hoc analysis of phase III open-label extension studies stratified by enzyme-inducing anti-seizure medication use

Rohit Marawar et al. Epilepsy Behav Rep. .

Abstract

Examine long-term findings from two Phase III open-label extension (OLEx) studies of adjunctive perampanel in patients aged ≥60 years experiencing focal seizures (FS), with/without focal to bilateral tonic-clonic seizures (FBTCS), with/without enzyme-inducing anti-seizure medications (EIASMs).

Methods: Study 307 (NCT00735397) included a Conversion Period (16 weeks; blinded) and a Maintenance Period (256 weeks). Study 335 OLEx (NCT01618695) included Pre-conversion (4 weeks), Conversion (6 weeks), and Maintenance Periods (≥46 weeks). Perampanel (2-12 mg/day) was given alongside 1-3 concomitant ASMs, of which ≤2 (Study 307) and ≤1 (Study 335) were EIASMs. Efficacy and safety outcomes were analyzed.

Results: Seventy-one patients aged ≥60 years were included in the Full and Safety Analysis Sets. Over 4 years, seizure frequency decreased regardless of EIASM use; seizure-freedom rates for FS were 0.0 % (n = 0/71) for Year 1, 2.6 % (n = 1/38) Year 2, 5.3 % (n = 1/19) Year 3, and 0.0 % (n = 0/14) Year 4. For FBTCS, these rates were 26.3 % (n = 5/19) for Year 1, 22.2 % (n = 2/9) Year 2, 40.0 % (n = 2/5) Year 3, and 0.0 % (n = 0/4) Year 4. The 90 % responder rates were ≥14.0 % for FS and ≥40.0 % for FBTCS. Incidence of treatment-emergent adverse events (TEAEs) was highest during Year 1 (87.3 % [n = 62/71]) but decreased across Years 2-4 (47.4 %-60.4 %). The most commonly reported TEAE during Years 1/2 was dizziness (47.9 % [n = 34/71] and 12.5 % [n = 6/48], respectively) and during Years 3/4 was fall (15.8 % [n = 3/19] and 14.3 % [n = 2/14]).

Significance: Adjunctive perampanel conferred long-term seizure control in older patients with epilepsy; safety was aligned with established perampanel safety profile.

Keywords: Adjunctive therapy; Epilepsy; Focal to bilateral tonic-clonic seizures; Older adults; Perampanel.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rohit Marawar has received grant support from Eisai; has been a clinical trial investigator for Xenon; has carried out consulting for Jazz Pharmaceuticals; has served on advisory boards for SK Life Science; has received speaker bureau honoraria for Neurelis. Ilo E. Leppik has no real or apparent conflicts of interest to disclose in relation to this work. Robert T. Wechsler has been a clinical trial investigator for Aquestive, Cerevel, Eisai, Eliem, Engage Pharmaceuticals, Epalex, Equilibre, Greenwich Biosciences, Jazz Pharmaceuticals, Otsuka, Receptor Neuroscience, SK Life Science, ThirdRock, UCB Pharmaceuticals, Xenon, and Zogenix; has served on advisory boards and/or carried out consulting work for Aquestive, Cerevel, Eisai, Engage Pharmaceuticals, Engrail, Greenwich Biosciences, Jazz Pharmaceuticals, Novella, Otsuka, SK Life Science, and UCB Pharmaceuticals; has received speaker bureau honoraria for Aquestive, Eisai, Jazz Pharmaceuticals, Neurelis, SK Life Science, and UCB Pharmaceuticals; has pay-for-call arrangements with St. Luke’s Health System in Boise, ID; has served as the medical director of the Epilepsy Center at St. Luke’s Health System in Boise, ID, and as the president of the Epilepsy Foundation of Idaho; and is a member of the Epilepsy Study Consortium and the Executive Committee of the Consortium of Private Epilepsy Centers. Anna Patten is an employee of Eisai Europe Ltd. Leock Y. Ngo is a former employee of Eisai Inc.

Figures

Fig. 1
Fig. 1
A) Median percent reduction in seizure frequency per 28 days from baseline over 4 years in patients aged ≥60 years, and B) median percent reduction in seizure frequency per 28 days from baseline over 4 years in patients aged ≥60 years, stratified by concomitant EIASM use recorded at baseline (Full Analysis Set). EIASM, enzyme-inducing anti-seizure medication; FBTCS, focal to bilateral tonic-clonic seizure; FS, focal seizure.
Fig. 1
Fig. 1
A) Median percent reduction in seizure frequency per 28 days from baseline over 4 years in patients aged ≥60 years, and B) median percent reduction in seizure frequency per 28 days from baseline over 4 years in patients aged ≥60 years, stratified by concomitant EIASM use recorded at baseline (Full Analysis Set). EIASM, enzyme-inducing anti-seizure medication; FBTCS, focal to bilateral tonic-clonic seizure; FS, focal seizure.
Fig. 2
Fig. 2
A) 50 % responder rates, B) 75 % responder rates, C) 90 % responder rates, and D) seizure-freedom rates over 4 years in patients aged ≥60 years (Full Analysis Set). FBTCS, focal to bilateral tonic-clonic seizure; FS, focal seizure.
Fig. 2
Fig. 2
A) 50 % responder rates, B) 75 % responder rates, C) 90 % responder rates, and D) seizure-freedom rates over 4 years in patients aged ≥60 years (Full Analysis Set). FBTCS, focal to bilateral tonic-clonic seizure; FS, focal seizure.
Fig. 2
Fig. 2
A) 50 % responder rates, B) 75 % responder rates, C) 90 % responder rates, and D) seizure-freedom rates over 4 years in patients aged ≥60 years (Full Analysis Set). FBTCS, focal to bilateral tonic-clonic seizure; FS, focal seizure.
Fig. 2
Fig. 2
A) 50 % responder rates, B) 75 % responder rates, C) 90 % responder rates, and D) seizure-freedom rates over 4 years in patients aged ≥60 years (Full Analysis Set). FBTCS, focal to bilateral tonic-clonic seizure; FS, focal seizure.
Fig. 3
Fig. 3
A) 50 % responder rates, B) 75 % responder rates, C) 90 % responder rates, and D) seizure-freedom rates over 4 years in patients aged ≥60 years, stratified by concomitant EIASM use recorded at baseline (Full Analysis Set). EIASM, enzyme-inducing anti-seizure medication.
Fig. 3
Fig. 3
A) 50 % responder rates, B) 75 % responder rates, C) 90 % responder rates, and D) seizure-freedom rates over 4 years in patients aged ≥60 years, stratified by concomitant EIASM use recorded at baseline (Full Analysis Set). EIASM, enzyme-inducing anti-seizure medication.
Fig. 3
Fig. 3
A) 50 % responder rates, B) 75 % responder rates, C) 90 % responder rates, and D) seizure-freedom rates over 4 years in patients aged ≥60 years, stratified by concomitant EIASM use recorded at baseline (Full Analysis Set). EIASM, enzyme-inducing anti-seizure medication.
Fig. 3
Fig. 3
A) 50 % responder rates, B) 75 % responder rates, C) 90 % responder rates, and D) seizure-freedom rates over 4 years in patients aged ≥60 years, stratified by concomitant EIASM use recorded at baseline (Full Analysis Set). EIASM, enzyme-inducing anti-seizure medication.
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