Abstracts

Rationale: Perampanel is a once-daily oral anti-seizure drug (ASD) for partial-onset seizures and primary generalized tonic-clonic seizures. In the US, 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 years. 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, 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 Safety Analysis Set (N=1693) included 41 (2.4%) patients aged <4 years (mean [standard deviation (SD)] age: 2.3 [0.82] years; 46.3% female; mean [SD] age at epilepsy diagnosis: 0.8 [1.6] years; mean [SD] time since epilepsy diagnosis: 2.8 [3.5] years). Seizure types included: myoclonic, n=22 (53.7%); generalized tonic-clonic, n=18 (43.9%); and complex partial, n=17 (41.5%). Most patients received 1–3 concomitant ASDs at Baseline (n=34 [82.9%]). Perampanel dose was titrated as follows: weekly (17.1% of patients), every 2 weeks (14.6%), ‘other’ (48.8%), and ‘unknown’ (19.5%). The mean (SD, range) maximum perampanel dose was 3.5 (2.1, 0–10) mg/day and the mean (SD, range) cumulative duration of exposure to perampanel was 11.6 (10.0, 0.0–37.5) months. At the end of the study, 20 (48.8%) pediatric patients aged <4 years were ongoing on perampanel and 21 (51.2%) had discontinued; primary reasons for discontinuing included inadequate therapeutic effect (n=9 [22.0%]) and adverse event (n=8 [19.5%]). Retention rates over 24 months are shown in Figure 1; at 24 months following treatment initiation, 5/14 (35.7%) patients remained on perampanel. Treatment-emergent adverse events were reported in 12 (29.3%) pediatric patients (<4 years); irritability (7.3%) and abnormal behavior (4.9%) were the most common. 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 years with epilepsy. However, it should be noted that perampanel is not currently approved for use in this age group. Funding: Eisai Inc.