(770) Efficacy and Safety of Perampanel as First Adjunctive Therapy after First or Second Monotherapy in Patients with Partial-Onset Seizures (POS): Post Hoc Analysis of the FAME Study
Professor in Neurology Korea University Guro Hospital, Guro-gu, Seoul, Republic of Korea
Rationale: In the U.S. 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. Analyses have shown that a high number of previous antiepileptic drugs (AEDs) may be a poor prognostic factor. We present a post hoc analysis from the FAME study (Fycompa as first Add-on to Monotherapy in pts with Epilepsy; Study 412, NCT02726074; South Korea) to assess the efficacy and safety of perampanel received as first-add on to first or second AED monotherapy. Methods: Patients in FAME were aged ≥ 12 years with POS with/without secondarily generalized seizures (SGS) and had failed 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, pts were stratified by first and second monotherapy use at baseline. Results: The Full Analysis Set included 79 pts receiving a first monotherapy and six pts a second monotherapy at baseline. First monotherapies were levetiracetam (n=31), carbamazepine (n=20), oxcarbazepine (n=14), lamotrigine (n=7), valproic acid (n=4), topiramate (n=2), and zonisamide (n=1). Second monotherapies were levetiracetam (n=3) and oxcarbazepine (n=3). For first monotherapy, perampanel doses were 4 mg/day (n=42; 53.2%), 6 mg/day (n=24; 30.4%), 8 mg/day (n=12; 15.2%), and 10 mg/day (n=1; 1.3%); for second monotherapy these were 6 mg/day (n=3; 50%), and 4, 10, and 12 mg/day (all n=1; 16.7%). For POS, 50% responder rates were 83.5% (n=66/79) and 33.3% (n=2/6) for first and second monotherapy, respectively (P=0.0134). Seizure-freedom rates were 50.6% (n=40/79) and 0% (n=0/6) for first and second monotherapy, respectively. Median percent reduction in POS frequency/28 days was 100.0% (n=78/79) and 21.8% (n=6/6) for first and second monotherapy, respectively (P=0.0039). Sixteen pts had SGS during baseline, all of whom received first monotherapy; 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 93 pts receiving first monotherapy and 9 a second monotherapy at baseline. TEAE incidence was similar in both groups; the most common for first and second monotherapy was dizziness (Table 1). Serious TEAEs occurred in 8 pts (first monotherapy, n=6; second monotherapy, n=2) and 14 pts discontinued due to a TEAE (first monotherapy, n=13; second monotherapy, n=1). Conclusions: Perampanel as first add-on to first or second monotherapy was associated with improvements in seizure response relative to baseline; however, the small number of pts in the second monotherapy group limits direct comparisons between first and second monotherapy. These data support the use of perampanel as an early-line treatment option. Funding: Please list any funding that was received in support of this abstract.:
