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

TL;DR

Perampanel helps reduce seizures in older adults over four years, with safety matching its known profile.

Contribution

Demonstrates long-term efficacy and safety of perampanel in older patients with focal seizures.

Findings

Older patients experienced a 95.5% median reduction in focal to bilateral tonic-clonic seizures in Year 1.

Safety profile of perampanel remained consistent with known effects over four years.

Common side effects included dizziness in early years and falls in later years.

Abstract

•Adjunctive perampanel conferred long-term seizure control in older patients.•During Year 1, older adults had a 95.5 % median percent reduction in FBTCS frequency.•The most common TEAEs were dizziness (Years 1/2) and fall (Years 3/4).•Adjunctive perampanel long-term safety was aligned with established safety profile.

Adjunctive perampanel conferred long-term seizure control in older patients.

During Year 1, older adults had a 95.5 % median percent reduction in FBTCS frequency.

The most common TEAEs were dizziness (Years 1/2) and fall (Years 3/4).

Adjunctive perampanel long-term safety was aligned with established safety profile.

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.

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