Assessment of the Long-Term Efficacy and Safety of Adjunctive Perampanel in Adolescent Patients: Post Hoc Analysis of Open-Label Extension (OLEx) Studies (P1.268)

Objective: To assess the long-term efficacy and safety of adjunctive perampanel in adolescent patients (aged ≥12 to ≤17 years) with secondarily generalized seizures (SGS) or primary generalized tonic-clonic seizures (PGTCS) from OLEx studies. Background: Perampanel is approved for treatment of partial seizures, with or without SGS, and adjunctive treatment of PGTCS in epilepsy patients aged ≥12 years. In Phase II/III randomized, double-blind, placebo-controlled studies, adjunctive perampanel (≤12 mg/day) demonstrated efficacy and tolerability in patients with partial seizures, with or without SGS, or PGTCS and idiopathic generalized epilepsy. Patients who completed these studies could enter OLEx studies: 307 (NCT00735397), 335 OLEx (NCT01618695), 235 OLEx (NCT01161524), and 332 OLEx (NCT02307578). Design/Methods: All OLEx studies comprised a blinded Conversion Period (6–16 weeks), when perampanel dose optimization was achieved (≤12 mg/day), and a Maintenance Phase (27–256 weeks; ≤1 to ≤5 years’ exposure). All patients received perampanel during the OLEx. Efficacy and safety assessments (for ≤4 years) included median percent change in seizure frequency per 28 days, 50% and 75% responder and seizure-freedom rates, and monitoring of treatment-emergent adverse events (TEAEs). Results: The Safety Analysis Set included 129 adolescent patients (SGS, n=109; PGTCS, n=19). Median percent reductions in seizure frequency per 28 days were 62.8% and 84.0% during Year 1, and 73.2% and 100.0% during Year 4 for SGS and PGTCS, respectively. Corresponding 50% responder rates were 56.9% and 63.2% (Year 1), and 65.2% and 100.0% (Year 4), respectively. For each seizure type, TEAE incidence was highest during the first year of perampanel exposure; the most common TEAEs were dizziness, somnolence, and nasopharyngitis. Conclusions: Long-term (up to 4 years) treatment with adjunctive perampanel (≤12 mg/day) was efficacious and well tolerated in adolescent patients with SGS or PGTCS. These post hoc results are encouraging, given the refractory nature of these seizure types. Study Supported by: Eisai Inc. Disclosure: Dr. Pina-Garza has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sunovion, UCB Pharma, Supernus, Lundbeck, Eisai. Dr. Villanueva has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with UCB, BIAL, EISAI, ESTEVE, NOVARTIS. Dr. Villanueva has received research support from UCB, BIAL, EISAI, ESTEVE. Dr. Rosenfeld has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Speaker’s Bureau UCB Pharma, Sunovion Pharmaceuticals, and Eisai. Dr. Rosenfeld has received research support from GW Pharmaceuticals, UCB Pharma, Medtronic, SK Life, Marinus, Upsher Smith and Takeda Pharmaceutical Company. Dr. Yoshinaga has nothing to disclose. Dr. Bibbiani has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai employee. Dr. Patten has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai Ltd. Dr. Williams has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Eisai Inc. Dr. Williams holds stock and/or stock options in Spouse is employee of Stryker Orthopedics. Dr. Williams has received research support from Employee of Eisai Inc. Dr. Laurenza has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai employee.