Assessment of the long-term efficacy and safety of adjunctive perampanel: pooled analyses of four open-label extension studies (P3.238)

Objective: To evaluate the long-term efficacy and safety of adjunctive perampanel in patients with secondarily generalized (SG) seizures or primary generalized tonic-clonic seizures (PGTCS) from four Phase II/III open-label extension (OLE) studies. Background: Perampanel is approved for adjunctive treatment of partial-onset seizures, with or without SG seizures, and for PGTCS in epilepsy patients aged ≥12 years. Phase II/III randomized, double-blind, placebo-controlled studies have demonstrated the efficacy and tolerability of adjunctive perampanel, and patients who completed the Double-blind Phase of these studies were eligible to enter OLEs. Design/Methods: All OLEs (Studies 207 [NCT00368472], 307 [NCT00735397], 335 OLE [NCT01618695], and 332 OLE [NCT02307578]) comprised a blinded Conversion Period (6–16 weeks across studies) followed by a Maintenance Phase (32–424 weeks; ≤1 to ≤8 years’ exposure, across studies). All patients received perampanel (maximum 12 mg/day) during the OLE, irrespective of prior treatment during the Double-blind Phase. Efficacy assessments included percent change in seizure frequency per 28 days and responder rates. Safety assessments included monitoring treatment-emergent adverse events (TEAEs). Results: Mean cumulative exposure to perampanel was 102.3 weeks for patients with SG seizures (n=720) and 83.9 weeks for patients with PGTCS (n=138); median percent reductions in seizure frequency were 66.7% and 80.6%, respectively. The corresponding 50%, 75%, and 100% responder rates were 59.5%, 45.3%, and 18.4% for patients with SG seizures, and 72.5%, 51.5%, and 16.7% for patients with PGTCS. For each seizure type, an improvement in efficacy from baseline was observed irrespective of treatment received during the Double-blind Phase. TEAEs occurred in 79.2% of patients with SG seizures, and 71.7% of patients with PGTCS. Conclusions: Long-term adjunctive treatment with perampanel demonstrated efficacy in patients with SG seizures or PGTCS, irrespective of prior treatment during the Double-blind Phase. Safety outcomes were consistent with the known safety profile of perampanel. Study Supported by: Eisai Inc. Disclosure: Dr. Rektor has nothing to disclose. Dr. Krauss has nothing to disclose. Dr. Inoue has nothing to disclose. Dr. Kaneko has nothing to disclose. Dr. Williams has received personal compensation for activities with Eisai, Inc. Dr. Patten has received personal compensation for activities with Eisa Ltd as an employee. Dr. Bibbiani has received personal compensation for activities with Eisai Inc. as an employee. Dr. Laurenza has received personal compensation for activities with Eisai Inc. as an employee. Dr. Wechsler has received personal compensation for activities with Cyberonics, Eisai, Sunovion, Marinus, and Lundbeck.