Abstracts

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

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 (further dose increases [of 2 mg] based on response and tolerability; maximum, 12 mg/day). Dose increases were ≥ 2 weeks for patients taking a non-enzyme-inducing anti-seizure medication (EIASM) and weekly 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 (Maintenance Period) included median percent reduction in seizure frequency/28 days and 50% responder rate.

Results: As of March 23, 2021, 23 patients with FOS (n=16 [FBTCS, n=1]) or GTCS (n=7) were included in the Safety Analysis Set. Of these, 12 had completed and 11 had discontinued: primary reasons for discontinuation (≥ 2 patients [n=FOS/FBTCS/GTCS]): adverse event (n=2/0/3), lost to follow-up (n=2/1/0), and patient choice (n=2/0/0). The Full Analysis Set included 10 patients: FOS (n=8 [FBTCS, n=0]) and GTCS (n=2). The mean (standard deviation [SD]) patient age was 37.8 (17.5), 26.0 (0.0), and 28.3 (9.3) years for patients with FOS, FBTCS, and GTCS, respectively. The mean (SD) daily perampanel dose (mg; Maintenance) by seizure type was: FOS, 6.0 (1.5); FBTCS, (no data), GTCS, 5.8 (3.2). Figure 1 shows retention rates at 3, 6, 9, and 12 months by seizure type; rates were approximately 40% for patients with FOS or GTCS at 12 months. Seizure freedom was achieved by one patient with FOS (16.7% [observed]), and a ≥ 50% reduction in seizure frequency was achieved by all four evaluable patients with FOS (100.0%; last observation carried forward [LOCF]). The median percent reduction/28 days in FOS frequency was 65.3% (n=4; LOCF). The sample size was too small to evaluate change in GTCS frequency. Treatment-emergent adverse events were reported in 13 (81.3%), 0 (0.0%), and 7 (100.0%) patients with FOS, FBTCS, and GTCS, respectively (Table 1).

Conclusions: These interim results of ELEVATE show that perampanel as monotherapy/first add-on was generally well tolerated with no unexpected safety concerns. Retention rates were approximately 40% for patients with FOS or GTCS at 12 months. 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.