Abstracts

Rationale: Perampanel is a once-daily, oral anti-seizure drug (ASD) for partial-onset seizures and primary generalized tonic-clonic seizures. In the United States, perampanel is licensed in pediatric patients aged ≥4 years who have partial-onset seizures, with or without secondarily generalized seizures. However, there is limited information on real-world use of perampanel as an ASD in pediatric patients. PROVE (Study 506; NCT03208660) is 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. Here, we report the results from a subgroup analysis of patients aged 4 to <12 years. Methods: Data were obtained from medical records across 21 sites in 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 200 (11.8%) patients aged 4 to <12 years (mean [standard deviation (SD)] age: 8.3 [2.3] years; median age: 9.0 years); female/male: 51.5%/48.5%. Epilepsy-specific medical history is shown in Table 1. Most patients received 1-3 concomitant ASDs at Baseline (n=144 [72.0%]). Perampanel dose was titrated: weekly (14.5% of patients), every 2 weeks (18.5%), every 3 weeks (3.0%), 'other' (54.0%), and 'unknown' (10.0%). The mean (SD, range) maximum perampanel dose was 5.3 (2.9, 0-16) mg/day and the mean (SD, range) cumulative duration of exposure to perampanel was 14.7 (13.4, 0.0-58.1) months. At the end of the study, 97 (48.5%) pediatric patients aged 4 to <12 years were ongoing on perampanel and 98 (49.0%) had discontinued; primary reasons for discontinuing included adverse events (n=35 [17.5%]) and inadequate therapeutic effect (n=29 [14.5%]). Retention rates on perampanel over 24 months are shown in Figure 1. Treatment-emergent adverse events (TEAEs) were reported in 62 (31.0%) pediatric patients (4 to <12 years); aggression (7.0%), somnolence (4.0%), and seizure (3.5%) were the most common. Twenty-six (13.0%) patients had mixed psychiatric symptoms reported as TEAEs that led to discontinuation of perampanel. Serious TEAEs occurred in 5 (2.5%) patients, including 2 (1.0%) deaths (considered unrelated to study drug). Conclusions: These results from PROVE suggest that daily oral doses of adjunctive perampanel are generally well tolerated, with favorable retention rates for up to 2 years in pediatric patients aged 4 to <12 years with epilepsy. Funding: Eisai Inc.