Efficacy and Safety of Eslicarbazepine Acetate According to Epilepsy Etiology: A Post-hoc Analysis of Three Phase III Trials in Adults with Focal Seizures (1559)

Objective: To evaluate the safety and efficacy of adjunctive eslicarbazepine acetate (ESL) in adults with focal seizures, according to epilepsy etiology. Background: ESL is a once-daily (QD), oral antiepileptic drug (AED) for focal (partial-onset) seizures. Design/Methods: Data were pooled from three Phase III, randomized, double-blind, placebo-controlled trials (2093–301, −302, −304). After an 8-week baseline period, adults with ≥4 focal seizures/month and taking 1–3 AEDs were randomized equally to receive placebo, ESL 400 mg (Studies 301 and 302 only; not reported here), ESL 800 mg or ESL 1200 mg QD (2-week titration; 12-week maintenance). Results: Epilepsy etiology categories (safety/efficacy analysis populations) included: other/unknown (n=526/520), idiopathic (n=255/239), cranial trauma/injury (n=166/164), congenital/hereditary disorders (n=109/106), and infectious disease (n=105/104). Responder (≥50% reduction from baseline in standardized seizure frequency) rates were dose-related for most etiologies. Patients with infectious disease (58.3%) and cranial trauma/injury (46.3%) etiologies had the highest responder rates with ESL 1200 mg; patients with congenital/hereditary disorders had the lowest (29.0%). Treatment-emergent adverse event (TEAE) incidences were generally higher with ESL than placebo but similar between ESL doses, across etiologies. Serious adverse events occurred in Conclusions: The efficacy of ESL was generally comparable across epilepsy etiologies (responder rates: 23–58%). Responder rates were higher with ESL than placebo and dose-related. Responder rates were highest in patients with epilepsy caused by infectious disease or cranial trauma/injury, and lowest in those with congenital/hereditary disorders. Incidences of TEAEs leading to ESL discontinuation were dose-dependent. TEAEs leading to ESL discontinuation and psychiatric TEAEs occurred most frequently in patients with congenital/hereditary disorders. Disclosure: Dr. Cantu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employment: Sunovion Pharmaceuticals Inc..Dr. Grinnell has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sunovion Pharmaceuticals Inc. Dr. Magalhaes has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employment: BIAL – Portela & Ca, S.A.. Dr. Loureiro has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employment: BIAL – Portela & Ca, S.A.. Dr. Loureiro has received research support from BIAL. Dr. Tosiello has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employment: Sunovion Pharmaceuticals Inc.. Dr. Blum has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sunovion Pharmaceuticals Inc. Dr. Blum has received research support from Sunovion Pharmaceuticals Inc.