Abstracts

Rationale: Perampanel, a selective, non-competitive AMPA receptor antagonist, is approved for treatment of partial seizures, with or without secondarily generalized seizures, and adjunctive treatment of primary generalized tonic-clonic seizures in patients with epilepsy aged ≥12 years. Currently, there is limited information regarding real-world use of perampanel in the US as an antiepileptic drug (AED), and such clinical data may inform patient management. Here, we report interim results from a Phase IV retrospective study to assess retention rate, safety, and dosing experience with perampanel administered during routine clinical care. Methods: Study 506 (NCT03208660) is an ongoing, multicenter, non-interventional study of patients with a diagnosis of epilepsy and who initiated perampanel treatment after January 1, 2014. Data were obtained from medical records and where available included: AED history; seizure frequency from seizure diaries/clinician assessments; perampanel titration and dosage, including maximum and average perampanel dose during treatment; safety data, including changes in height (pediatric patients) and body weight, treatment-emergent adverse events (TEAEs), and serious adverse events. Based on the Safety Analysis Set (SAS), the primary endpoint is retention rate, defined as the proportion of patients remaining on perampanel at 3, 6, 12, 18, and 24 months following treatment initiation. Safety and dosing experience were assessed as secondary objectives. Results: The SAS for this interim analysis included 187 patients with epilepsy (mean age [standard deviation (SD)]: 26.7 [14.3] years; female: 51.3%; mean [SD] time since diagnosis: 17.5 [11.8] years; ILAE seizure classification: partial: 49.2%; idiopathic generalized epilepsy: 23.0%; other: 24.1%; unknown: 3.7%). The majority of patients received 1–3 concomitant AEDs (82.4%) of whom 17.1% were taking enzyme-inducing AEDs at Baseline. The mean (SD, range) maximum perampanel dose was 7.1 (2.9, 1.5–20.0) mg, and mean (SD) cumulative duration of exposure to perampanel was 15.4 (12.9) months (Table 1). Retention rates at various time points are shown in Figure 1; at 24 months following treatment initiation, 58.5% of patients remained on perampanel. A total of 75 (40.1%) patients discontinued treatment due to adverse events (25.1%), inadequate therapeutic effect (10.2%), other reasons (3.2%), unknown reasons (1.1%), or patient choice (0.5%). Dizziness (9.1%), somnolence (5.3%), and aggression (4.3%) were the most commonly reported TEAEs.  Conclusions: An interim analysis of Study 506 found that over half of epilepsy patients receiving perampanel and who were followed for 24 months (n=48/82; 58.5%) as part of routine clinical care remained on treatment. Perampanel (1.5–20.0 mg) was administered to patients of different ages with multiple seizure types. It is anticipated that additional interim analyses will provide invaluable real-world information on retention rate, safety, and dosage profile of perampanel administered in clinical practice.  Funding: Eisai Inc.