Abstracts

Rationale: In the US and Europe, perampanel is approved for focal-onset seizures (FOS), with/without focal to bilateral tonic-clonic seizures (FBTCS), in patients aged ≥ 4 years (US: monotherapy/adjunctive; Europe, adjunctive), and generalized tonic-clonic seizures in patients aged ≥ 12 (≥ 7, Europe) years (adjunctive). Adjunctive perampanel 4 mg/day has been shown to be efficacious for FOS (with/without FBTCS) in a pooled post hoc analysis of four Phase 3 studies. The AMPA Study (defined in title; NCT04257604; Study 501) investigated the effectiveness of adjunctive perampanel in patients with FOS (with/without FBTCS) in a real-life setting in Italy. Here, we report a post hoc analysis of the efficacy and safety of perampanel used at a dose of 4 mg/day from the AMPA study.

Methods: The AMPA study was a multicenter, prospective, real-life, observational study of perampanel as adjunctive therapy in patients aged ≥ 12 years with FOS, with or without FBTCS. Patients with insufficiently controlled seizures while receiving 1–3 anti-seizure medications (ASMs) were prescribed adjunctive perampanel in line with the approved indication; the treating physician’s decision to prescribe perampanel was made before and independently of their decision to include the patient in the study. Seizure diaries and treatment-emergent adverse events (TEAEs) were verified at study visits (baseline and after 3/6/12 months of treatment). The primary endpoint was percentage change from baseline in seizure frequency per 28 days at Month 6 (secondary endpoint, Month 12); other secondary endpoints included 50% and 75% responder rates, seizure-freedom rates, retention rates, and monitoring of TEAEs up to 12 months.

Results: Of the 234 patients who were administered adjunctive perampanel, 62 (26.5%; Safety Analysis Set) received perampanel 4 mg/day as modal dose. Median reduction from baseline in all-seizure frequency with perampanel 4 mg/day was 55.4% (95% confidence interval [CI], 31.7%–90.3%) at Month 6 and 63.9% (95% CI, 31.7%–89.2%) at Month 12. The 50% and 75% responder and seizure-freedom rates with perampanel 4 mg/day were sustained over the course of the 12-month treatment period (Table 1). At Months 6 and 12, retention rates with perampanel 4 mg/day were 62.9% (n=39/62) and 46.8% (n=29/62), respectively (Table 1). The overall incidence of TEAEs with perampanel 4 mg/day was 50.0% (n=31/62); 8 (12.9%) patients experienced serious TEAEs with no deaths reported during the study (Table 2). Fifteen (24.2%) patients discontinued due to TEAEs; 10 (16.1%) patients who were receiving perampanel 4 mg/day had a dose reduction due to TEAEs. The most common TEAEs were: dizziness/vertigo (17.7% [n=11]); behavior disorder (6.5% [n=4]); somnolence (4.8% [n=3]).

Conclusions: Based on the findings of this analysis, adjunctive perampanel at a low dose of 4 mg/day in a real-life clinical setting was efficacious in patients aged ≥ 12 years with FOS (with/without FBTCS); no new safety signal emerged.

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