FAME study: Efficacy and safety of perampanel as first adjunctive therapy after first or second monotherapy in patients with focal-onset seizures

초록

Purpose: In the US/Korea, perampanel is approved for focal-onset seizures (FOS) (adjunctive/monotherapy) in patients aged ≥4 years and generalised tonic-clonic seizures (adjunctive) in patients aged ≥12 (≥7, Korea) years. This post hoc analysis of the open-label, single-arm FAME study (NCT02726074) explored whether the efficacy and safety of first adjunctive perampanel is impacted by the number of previous monotherapies (one or two). Method: Patients in FAME were aged ≥12 years with FOS with/without focal to bilateral tonic-clonic seizures (FBTCS) and had failed antiepileptic drug monotherapy. Perampanel was up-titrated to ≤12 mg/day (12 weeks), followed by a 24-week Maintenance Period. Endpoints included 50% responder/seizure-freedom rates, median percent change in seizure frequency/28 days and treatment-emergent adverse events (TEAEs). For this analysis, endpoints were stratified by whether the prior treatment was a first or second monotherapy. Results: The Full Analysis Set included 79 patients receiving perampanel 4–10 mg/day with first monotherapies (most commonly: levetiracetam [n = 31]; carbamazepine [n = 20]; oxcarbazepine [n = 14]) and six receiving perampanel 6–12 mg/day with second monotherapies (levetiracetam [n = 3]; oxcarbazepine [n = 3]). For first vs second monotherapy, 50% responder rates were 83.5% (n = 66/79) vs 33.3% (n = 2/6; P = 0.0134), seizure-freedom rates were 50.6% (n = 40/79) vs 0.0% (n = 0/6; P = 0.0274) and median percent reductions in seizure frequency/28 days were 100.0% vs 21.8% (P = 0.0039). In patients with FBTCS (all first monotherapy), the seizure-freedom rate was 75.0% (n = 12/16). In the Safety Analysis Set, TEAE profiles were similar with first vs second monotherapy (TEAE incidence: 75.3% [n = 70/93] vs 77.8% [n = 7/9]; serious TEAEs: 6.5% [n = 6/93] vs 22.2% [n = 2/9]; discontinuations due to TEAEs: 14.0% [n = 13/93] vs 11.1% [n = 1/9]; most common TEAE in both groups: dizziness). Conclusion: Adjunctive perampanel was associated with improved seizure control following first or second monotherapy. However, the small number of patients on their second monotherapy limits comparisons. These data support early-line perampanel use. Funding: Eisai Korea Inc.