Abstracts

Rationale: Perampanel is a once-daily, oral anti-seizure drug (ASD) for partial-onset seizures and primary generalized tonic-clonic seizures. There are limited data on real-world use of perampanel as an ASD in the US. Here, we report the results from PROVE (Study 506; NCT03208660), a retrospective, multicenter, non-interventional Phase IV study assessing retention rate, safety, efficacy, and dosing experience of perampanel administered to patients with epilepsy during routine clinical care. Methods: Data were obtained from medical records of patients who initiated perampanel treatment after January 1, 2014. Follow-up was completed on March 15, 2019. Based on the Safety Analysis Set (SAS), the primary endpoint was 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. Results: The SAS (N=1693) included 1152 (68.0%) patients aged >=18 years, 292 (17.3%) aged 12 to <18 years, and 241 (14.3%) aged <12 years. Mean (standard deviation [SD]) patient age was 28.5 (16.5) years; 52.7% female. Median (minimum, maximum) time since diagnosis of epilepsy was 12 (0.0, 83.3) years; 1260 (74.4%) patients received 1-3 concomitant ASDs at Baseline. At the end of the study, 859 (50.7%) patients were ongoing on perampanel; 811 (47.9%) had discontinued. The most common primary reasons for discontinuation were adverse event (AE; n=332 [19.6%]) and inadequate therapeutic effect (n=213 [12.6%]). Perampanel dose was titrated: weekly (18.7%), every 2 weeks (18.7%), every 3 weeks (1.7%), 'other' (52.0%), and 'unknown' (8.9%). Mean (SD, range) cumulative duration of exposure was 17.1 (15.6, 0.0-77.1) months. Mean (SD, range) maximum perampanel dose was 6.6 (3.4, 0-52) mg/day. Retention rate on perampanel over 24 months is shown in Figure 1. At Months 22-24, median reduction in seizure frequency per 28 days was 89.4%; 50% responder rate was 76.5%, and 39.2% of patients achieved seizure freedom. Treatment-emergent AEs (TEAEs) occurred in 671 (39.6%) patients; the most common were dizziness (n=123 [7.3%]) and aggression (n=88 [5.2%]); 538 (31.8%) patients had TEAEs requiring dose adjustment. Serious TEAEs occurred in 68 (4.0%) patients, including 13 (0.8%) deaths. Conclusions: This analysis of PROVE 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.