Abstracts

Rationale: Perampanel is a once-daily oral antiepileptic drug (AED) for partial-onset seizures and primary generalized tonic-clonic seizures. There are limited data on real-world use of perampanel in the US as an AED. Study 506 (NCT03208660) is a retrospective, multicenter, non-interventional Phase IV study assessing retention rate, safety, and dosing experience of perampanel administered to epilepsy patients during routine clinical care. Here, we report the results from a second interim analysis. Methods: Study 506 is ongoing and involves patients who initiated perampanel treatment after January 1, 2014. Data were obtained from medical records for perampanel exposure, efficacy, and safety. Based on the Safety Analysis Set, the primary endpoint is retention rate (proportion of patients remaining on perampanel at 3, 6, 12, 18, and 24 months following treatment initiation). Safety, efficacy, and dosing experience were secondary objectives. Data cut-off date for this analysis was March 5, 2018. Results: The interim Safety Analysis Set (n=605) included 430 (71.8%) patients aged =18 years, 68 (11.4%) aged <12 years, and 101 (16.9%) patients aged 12 to <18 years. No information regarding age was available for 6 patients. Mean (standard deviation) patient age was 29.6 (16.4) years and 55.9% of patients were female. Median (min, max) time since diagnosis of epilepsy was 14.6 (0.0, 65.0) years. Most patients (n=490 [81.0%]) received 1–3 concomitant AEDs at Baseline. At data cut-off, 317 (52.4%) patients were ongoing on perampanel; 285 (47.1%) patients had discontinued. The most common primary reasons for discontinuation were adverse event (n=157 [26.0%]) and inadequate therapeutic effect (n=86 [14.2%]).The most common modal daily doses of perampanel received were 4 mg (n=116 [19.2%]), 6 mg (n=108 [17.9%]), and 8 mg (n=79 [13.1%]). Median (min, max) cumulative duration of exposure to perampanel was 10.8 (0.0, 66.9) months. Median (min, max) maximum perampanel dose was 6 (1, 20) mg. Retention rate on perampanel over 24 months was 49.8% (Figure 1).At Months 22–24, median reduction in seizure frequency per 28 days was 93.3% (n=27), 50% responder rate was 77.8% (n=21/27), and 40.7% (n=11/27) patients achieved seizure-free status. Investigators reported improvement, no change, or worsening of seizures in 57.3%, 29.5%, and 13.2% of patients, respectively.Treatment-emergent adverse events (TEAEs) occurred in 304 (50.2%) patients; the most common were dizziness (n=62 [10.2%]), aggression (n=37 [6.1%]), and irritability (n=30 [5.0%]). TEAEs leading to perampanel dose adjustments occurred in 239 (39.5%) patients. Serious TEAEs occurred in 14 (2.3%) patients, including 3 (0.5%) deaths. Conclusions: This interim analysis of Study 506 demonstrates favorable retention rates and sustained efficacy of perampanel for up to 2 years in patients with epilepsy treated during routine clinical care. Funding: Eisai Inc.