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

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.