(976) Efficacy and Safety of Perampanel as First Adjunctive Therapy in Patients with Partial-Onset Seizures: Post Hoc Analysis of the FAME Study by First-Line Antiepileptic Drug and Perampanel Dose
Head of Medical, Medical Dept. Eisai Korea Inc., Seoul, Republic of Korea
Rationale: In the U.S. and Korea, perampanel is approved for partial-onset seizures (POS; adjunctive and monotherapy) in patients (pts) aged ≥ 4 years (yrs), and adjunctive treatment of primary generalized tonic-clonic seizures in pts aged ≥ 12 (≥ 7, Korea) yrs. 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 outcomes of perampanel by dose in pts receiving different first-line antiepileptic drugs (AEDs). Methods: Patients in FAME were aged ≥ 12 yrs with POS with/without secondarily generalized seizures (SGS) and had failed on AED monotherapy. Perampanel was up-titrated to ≤ 12 mg/day (12 weeks), 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, endpoints were stratified by first-line AED and by perampanel maintenance dose. Results: The Full Analysis Set included 85 pts with POS with/without SGS. Perampanel maintenance doses were taken at 4 mg/day (n=43), 6 mg/day (n=27), 8 mg/day (n=12), 10 mg/day (n=2), and 12 mg/day (n=1). Concomitant AEDs taken at baseline included: levetiracetam (n=34), carbamazepine (n=20), oxcarbazepine (n=17), lamotrigine (n=7), and valproic acid (n=4). Table 1 shows responder rates and percent reduction in seizure frequency/28 days by concomitant AED use and perampanel dose. Overall, the 50% responder rate was highest when perampanel 4 mg/day was added to any of the 5 AEDs: levetiracetam (85.0%, n=17/20), carbamazepine (100.0%, 7/7), oxcarbazepine (100.0%, n=7/7), lamotrigine (100.0%; n=6/6), and valproic acid (100.0%; n=2/2). Adding 4 mg/day perampanel to carbamazepine (71.4%, 5/7), oxcarbazepine (85.7%, 6/7) or valproic acid (100.0%, 2/2); and 6 mg/day to oxcarbazepine (71.4%, 5/7) produced the highest seizure-freedom rates. Overall, the greatest median percent reduction in seizure frequency/28 days was with perampanel 4 mg/day and this was across all five AEDs analyzed (range, 96.9–100%). The Safety Analysis set comprised 102 pts, which included, 39 (38.2%), 23 (22.5%), 18 (17.6%), 9 (8.8%), and 6 (5.9%) pts who received levetiracetam, carbamazepine, oxcarbazepine, lamotrigine, and valproic acid, respectively. Table 2 shows TEAEs by concomitant AED use and perampanel dose. The most common TEAE was dizziness and overall this was observed most frequently with the 4 mg/day dose of perampanel. Eight pts reported a serious adverse event (SAE); one SAE of suicidal ideation with perampanel 4 mg/day and levetiracetam was considered possibly related to treatment; all other SAEs were considered unrelated to treatment. Conclusions: Perampanel at low doses (e.g., 4–6 mg/day) was effective in achieving seizure control and response with favorable tolerability in pts with POS regardless of first-line concomitant AED use. Funding: Please list any funding that was received in support of this abstract.:
