Abstracts

Rationale:
In the US and Korea, perampanel is approved for POS (adjunctive and monotherapy) in patients (pts) aged ≥ 4 years, and adjunctive treatment of primary generalized tonic-clonic seizures in pts aged ≥ 12 (≥ 7, Korea) years. We present results of a post hoc subgroup analysis from the FAME study (Fycompa as first Add-on to Monotherapy in pts with Epilepsy; Study 412, NCT02726074) to assess the efficacy and safety of low- and high-maintenance doses of adjunctive perampanel in pts with POS.
Method:
Pts in FAME were aged ≥ 12 yrs with POS with/without secondarily generalized seizures (SGS) and had failed antiepileptic drug monotherapy. Perampanel was up-titrated to ≤ 12 mg/day (12 weeks) based on investigator judgment of efficacy/tolerability, followed by a 24-week Maintenance Period. Endpoints included 50% responder and seizure-freedom rates, median percent change in seizure frequency/28 days, and treatment-emergent adverse events (TEAEs). For this analysis, pts were stratified by low-dose (4 and 6 mg/day) and high-dose (8, 10, and 12 mg/day) perampanel.
Results:
The Full Analysis Set included 85 pts with POS (16 had SGS). For pts with POS, 70 (82.4%) received low-dose perampanel (4 mg/day, n=43 [61.4%]; 6 mg/day, n=27 [38.6%]) and 15 (17.6%) received high-dose (8 mg/day, n=12 [80%]; 10 mg/day, n=2 [13.3%]; 12 mg/day, n=1 [6.7%]). All 16 pts with SGS received low-dose perampanel. During Maintenance, in pts with POS (with/without SGS), the 50% responder rate for low-dose perampanel was 88.6% (n=62/70) vs 40.0% (n=6/15) for high-dose (P=0.0002); seizure-freedom rate was 54.3% (n=38/70) for low-dose vs 13.3% (n=2/15) for high-dose perampanel (P=0.0039) (Figure 1). Median percent reduction during Maintenance in POS (with/without SGS) frequency/28 days was 100.0% (n=69/70) for low-dose vs 16.7% (n=15/15) for high-dose perampanel (P=0.0001). In the subset of pts with POS and SGS, 50% responder and seizure-freedom rates were 87.5% (n=14/16) and 75.0% (n=12/16), respectively. The Safety Analysis Set included 88 pts; 73 (83.0%) on low-dose and 15 (17.0%) on high-dose perampanel. Sixty-five (73.9%) pts reported TEAEs; Table 1 shows TEAEs by low- and high-dose perampanel. Six pts experienced a serious TEAE (low-dose, n=5; high-dose, n=1); 4 pts discontinued due to a TEAE (all low-dose perampanel). One case of suicide attempt was reported with low-dose perampanel (4 mg/day) in a pt with no prior psychiatric history; the TEAE was not considered related to perampanel.
Conclusion:
Seizure improvements were seen with low (4 and 6 mg/day) and high perampanel maintenance doses (8, 10, and 12 mg/day). Perampanel was generally well tolerated in both dose groups. These results suggest that some pts may achieve seizure control with lower perampanel doses; however, others may require up-titration to a higher dose based on response. Interpretation of these data should consider the higher number of pts in the low- vs high-dose groups.
Funding:
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Funding:
: Eisai Korea Inc.