Abstracts

Rationale: In the U.S. and Japan, perampanel is approved as monotherapy and adjunctive therapy for focal-onset seizures (FOS), with or without focal to bilateral tonic-clonic seizures (FBTCS), in patients aged ≥ 4 years, and for adjunctive treatment of generalized tonic-clonic seizures in patients aged ≥ 12 years. To assess the long-term efficacy and safety of perampanel, patients with FOS, with or without FBTCS, who completed placebo-controlled Phase III studies of adjunctive perampanel could enter OLEx Studies 307 (NCT00735397) and 335 OLEx (NCT01618695). Here, we report the long-term (up to 4 years) efficacy and safety of perampanel in a post hoc analysis of older patients aged ≥ 60 years with FOS, with or without FBTCS, from these OLEx studies.

Methods: Study 307 comprised a 16-week blinded Conversion Period and a 256-week Maintenance Period. Study 335 OLEx comprised 4-week Pre-conversion, 6-week Conversion, and ≥ 46-week Maintenance Periods. During the OLEx studies, patients received perampanel 2–12 mg/day. Efficacy assessments included median percent reduction in seizure frequency/28 days vs. pre-perampanel baseline, and 50% and 90% responder and seizure-freedom rates at Years 1, 2, 3, and 4. Safety assessments included monitoring of treatment-emergent adverse events (TEAEs).

Results: The Safety Analysis Set included 71 older patients aged ≥ 60 years with FOS (mean [standard deviation] age at date of informed consent, 64.0 [3.8] years; female, 60.6%); of these, 19 patients had FOS with FBTCS. At baseline, 11.3% (n=8), 46.5% (n=33), and 42.3% (n=30) of patients received 1, 2, or 3 anti-seizure medications, respectively. Reductions in seizure frequency were observed over 4 years; in Year 4, 64.3% of patients with FOS and 50.0% of patients with FBTCS achieved a ≥ 50% reduction and 28.6% and 50.0%, respectively, achieved a ≥ 90% reduction in seizure frequency (Figure 1). Seizure-freedom rates for total FOS during Years 1, 2, 3, and 4 were 0.0% (n=0/71), 2.6% (n=1/38), 5.3% (n=1/19), and 0.0% (n=0/14), and for FBTCS were 26.3% (n=5/19), 22.2% (n=2/9), 40.0% (n=2/5), and 0.0% (n=0/4), respectively; however, the small patient numbers at later time points should be taken into consideration when interpreting these data. During Years 1, 2, 3, and 4, respectively, 87.3% (n=62/71), 60.4% (n=29/48), 47.4% (n=9/19), and 57.1% (n=8/14) of patients experienced TEAEs; treatment-related TEAEs were observed in 84.5% (n=60/71), 31.3% (n=15/48), 21.1% (n=4/19), and 21.4% (n=3/14) of patients during Years 1, 2, 3, and 4 respectively. The most common TEAE during Years 1 and 2 was dizziness (n=34 [47.9%] and n=6 [12.5%], respectively), and during Years 3 and 4 was fall (n=3 [15.8%] and n=2 [14.3%], respectively).

Conclusions: In this post hoc analysis of adjunctive perampanel in older patients aged ≥ 60 years from Studies 307 and 335 OLEx, reductions in seizure frequency were observed over 4 years for both FOS and FBTCS; the safety profile was consistent with the overall populations, and no new safety signals emerged.

Funding: Eisai Inc.