Associate Regional Medical Director
Neurology Franchise Eisai Singapore Pte. Ltd., Singapore
Rationale: In the U.S., perampanel is approved for partial-onset seizures (POS; adjunctive and monotherapy) in patients aged ≥ 4 years, and adjunctive treatment of primary generalized tonic-clonic seizures in patients aged ≥ 12 years. The aim of this analysis was to review the effectiveness of perampanel for the treatment of secondarily generalized seizures (SGS) in two open-label studies. Methods: Study 342 (NCT03201900; FREEDOM) was a single-arm, Phase III study to assess perampanel monotherapy 4 mg/day during the Treatment Phase (6-week Titration and 26-week Maintenance Periods); perampanel could be titrated to 8 mg/day for an additional 30-week Treatment Phase if patients experienced a seizure during the 4 mg/day Maintenance Period. The primary endpoint was seizure-freedom rate during the Maintenance Period (4 mg/day and last evaluated dose [4 or 8 mg/day]). Study 412 (NCT02726074; FAME) was a single-arm, Phase IV, prospective cohort study of perampanel as first anti-seizure medication add-on therapy. During a 12-week Titration Period, perampanel dose was increased by 2 mg/day at ≥ 2-week intervals up to 12 mg/day. Patients then entered a 24-week Maintenance Period. Seizure-freedom rate in patients with SGS was a secondary endpoint. Both studies included patients aged ≥ 12 years with a diagnosis of epilepsy and POS, with/without SGS. Treatment-emergent adverse events (TEAEs) were monitored during both studies. In this analysis, we present perampanel efficacy and safety data for the treatment of SGS. Results: In Study 342, 57/89 (64.0%) patients in the Intent-to-Treat population (ITT; patients who received ≥ 1 dose of perampanel with ≥ 1 post-dose efficacy assessment) had SGS at baseline, and 48 patients with SGS went on to enter the 4 mg/day Maintenance Period (modified ITT). Seizure-freedom was achieved by 31/48 (64.6%) patients (Table 1). In Study 412, 16/85 (18.8%) patients in the Full Analysis Set (patients who received ≥ 1 dose of perampanel with ≥ 1 post-dose efficacy assessment) had SGS at baseline. Seizure-freedom was achieved by 12/16 (75.0%) patients (Table 1). In Study 342, 39/52 (75.0%) patients with SGS in the Safety Analysis Set experienced TEAEs; 28 (53.8%) patients experienced treatment-related TEAEs (Table 2). The most commonly reported TEAEs were dizziness (n=19, 36.5%), somnolence (n=8, 15.4%), and nasopharyngitis (n=6, 11.5%). In Study 412, 13/16 (81.3%) patients experienced TEAEs; 9 (56.3%) patients had TEAEs that were possibly treatment related (Table 2). The most commonly reported TEAE was dizziness (n=8, 50.0%). Conclusions: Perampanel administered as monotherapy in Study 342 or as first add-on therapy in Study 412 was efficacious for the treatment of patients with SGS, with an acceptable safety profile. Funding: Please list any funding that was received in support of this abstract.:
