Abstracts

Rationale: Seizure freedom with a patient’s first anti-seizure medication (ASM) is achieved by ~50% of patients. Perampanel is a once-daily oral ASM for FOS, with/without focal to bilateral tonic-clonic seizures (FBTCS), and GTCS. We assess the efficacy and safety of perampanel received as first add-on in patients from Studies 412 (NCT02726074; FAME; Korea), 501 (NCT04257604; AMPA; Italy), and 410 (NCT03288129; ELEVATE; US).

Methods: Patients in Studies 412 and 501 were aged ≥ 12 years with FOS (with/without FBTCS). In the Phase IV Study 412, patients received open-label perampanel as first add-on (up to 12 mg/day; 12-week Titration; 24-week Maintenance). Study 501 included patients prescribed perampanel (up to 12 mg/day) during routine clinical care over 12 months. Study 410 was a Phase IV open-label study of perampanel (up to 12 mg/day) in patients aged ≥ 4 years with FOS (with/without FBTCS) or GTCS (up to 13-week Titration; 39-week Maintenance). Primary endpoints were 50% responder rate (Study 412), median percent change in seizure frequency/28 days (Study 501), and retention rate (Study 410); secondary/exploratory endpoints included 75% responder rates, seizure-freedom rates, and treatment-emergent adverse events (TEAEs). Only patients receiving perampanel as first add-on were included in these analyses.

Results: In Study 412, 80/106 enrolled patients completed the study; 85 patients with FOS, including 16 with FBTCS, were included in the Full Analysis Set. The most common concomitant ASMs were levetiracetam (n=34 [40.0%]), carbamazepine (n=20 [23.5%]), and oxcarbazepine (n=17 [20.0%]). In Study 501, 11/240 enrolled patients received perampanel as first add-on therapy, of whom 8 were included in the Full Analysis Set (Intent-to-Treat). The most common concomitant ASM was carbamazepine (n=5 [45.5%]). In Study 410, 21/28 patients received perampanel as first add-on therapy; analyses of this subpopulation are ongoing and will be included in the final presentation. Median reduction from baseline in FOS (with/without FBTCS) frequency/28 days was 95.0% in Study 412 (100.0% for patients with FBTCS). In Study 501, median reduction in all-seizure frequency was 67.0%, 61.5%, and 61.5% at Months 3, 6, and 12, respectively. In Study 412, 50% responder rates were 68/85 (80.0%; 95% confidence interval [CI] 69.9, 87.9) and 14/16 (87.5%; 95% CI 61.7, 98.5) for FOS and FBTCS, respectively; in Study 501, these were 71.4%, 62.5%, and 62.5% for all seizures at Months 3, 6, and 12, respectively. 75% responder and seizure-freedom rates for Studies 412 and 501 are summarized in Table 1. A summary of TEAEs in Studies 412 and 501 is presented in Table 2.

Conclusions: Based on the available data from Studies 412 and 501, perampanel was found to be efficacious and generally safe and well tolerated in patients receiving perampanel as a first adjunctive ASM. These data support the use of perampanel as an early-line treatment option for patients with FOS (with/without FBTCS).

Funding: Please list any funding that was received in support of this abstract.: Eisai Korea Inc., Eisai S.r.l., Eisai Inc.