Abstracts

Rationale: In the US, perampanel is approved for the treatment of FOS in patients aged ≥ 4 years (adjunctive/monotherapy) and GTCS in patients aged ≥ 12 years (adjunctive). ELEVATE (Study 410; NCT03288129) was a multicenter, open-label, Phase IV study of perampanel monotherapy or first adjunctive therapy in patients aged ≥ 4 years with FOS, with/without focal to bilateral tonic-clonic seizures (FBTCS), or GTCS. We present interim efficacy and safety results from ELEVATE by seizure type and patient age (18−64 and > 64 years).

Methods: The study consisted of Screening, Titration (≤ 13 weeks), Maintenance (39 weeks), and Follow-up (4 weeks) Periods. During Titration, patients received perampanel at 2 mg/day, which was titrated to 4 mg/day (dose increases [by 2 mg] based on response and tolerability; maximum, 12 mg/day). Perampanel dose increases were ≥ 2 weeks apart for patients on monotherapy or for those taking a non-enzyme-inducing anti-seizure medication (EIASM), and weekly (if needed) for those taking an EIASM. The primary endpoint was retention rate at 3, 6, 9, and 12 months. Secondary endpoints included seizure freedom (Maintenance Period) and safety. Exploratory endpoints included median percent reduction in seizure frequency/28 days and 50% responder rate during the Maintenance Period.

Results: As of March 23, 2021, the Safety Analysis Set included 23 patients. The age and seizure type of these patients were: < 18 years (n=1; GTCS [data not presented]); 18−64 years (n=19; 13 FOS [of which 1 patient had FBTCS], 6 GTCS); and > 64 years (n=3, all FOS). Figure 1 shows retention rates at 3, 6, 9, and 12 months by age (18−64 and > 64 years) and by seizure type. Retention rates at 12 months were 46.2% (n=6/13) and 0.0% (n=0/3) for patients with FOS aged 18−64 years and > 64 years, respectively. Five patients had baseline and postbaseline seizure data and so were included in the efficacy analysis. Seizure freedom was achieved by one patient with FOS in the 18−64 age group (n=1/5; 20.0% [observed]); no patients in the > 64 age group achieved seizure freedom. Three patients in the 18−64 age group (3/3; 100.0%; [last observation carried forward [LOCF]) and one patient in the > 64 age group (1/1; 100.0% [LOCF]) with FOS achieved a ≥ 50% reduction in seizure frequency. The median percent reduction/28 days in total FOS frequency (LOCF) was 55.6% (n=3) and 90.7% (n=1) for patients aged 18−64 years and > 64 years, respectively. Treatment-emergent adverse events were reported by > 75.0% of patients across seizure types and age groups (Table 1).

Conclusions: These interim results of ELEVATE show that perampanel as monotherapy or first add-on was generally well tolerated across all age groups and seizure types studied. Some patients experienced improvements in seizure frequency from baseline regardless of age. Retention rates at 12 months were ≥ 33.3% for patients aged 18−64 years with FOS or GTCS. Additional analyses are being conducted and will be included in the presentation.

Funding: Please list any funding that was received in support of this abstract.: Eisai Inc.