Efficacy of lacosamide monotherapy in patients with newly diagnosed epilepsy stratified by baseline disease severity: sub-analysis of data from a prospective non-inferiority trial versus controlled-release carbamazepine (P5.227)

Objective: To evaluate efficacy and safety of lacosamide versus carbamazepine controlled-release (carbamazepine-CR) based on disease severity (≤2 or >2 seizures during 3-months pre-enrolment). Background: In a double-blind trial (SP0993; NCT01243177), lacosamide was non-inferior to carbamazepine-CR, as assessed by 6-month seizure-freedom, in patients with newly-diagnosed epilepsy experiencing focal or generalized tonic-clonic seizures. Design/Methods: Patients (≥16 years) were randomized 1:1 to twice-daily lacosamide/carbamazepine-CR, with strata defined by seizure-count (≤2 or >2) during 3-months prior to enrolment. Flexible dosing (lacosamide: 200/400/600mg/day; carbamazepine-CR: 400/800/1200mg/day) was based on seizure control. Outcomes included 6 and 12-month seizure-freedom at last-evaluated-dose. Current sub-analyses were performed for full analysis set (FAS) and per-protocol set (PPS). Results: 886 patients received trial medication (FAS); 448 were in ≤2 prior seizures stratum (lacosamide: 224; carbamazepine-CR: 224 [PPS: 204; 202]) and 438 were in >2 prior seizures stratum (220; 218 [PPS: 204; 195]). Among patients with ≤2 prior seizures, Kaplan-Meier estimated 6-month seizure-freedom was similar for lacosamide versus carbamazepine-CR (FAS: 94.3%; 94.1% [PPS: 95.4%; 95.3%]); 78.1% of lacosamide-treated and 74.1% of carbamazepine-CR-treated patients completed 6-months without seizure. Kaplan-Meier estimated 12-month seizure-freedom (FAS) was 79.8% with lacosamide versus 86.3% with carbamazepine-CR. Among patients with >2 prior seizures, Kaplan–Meier estimated 6-month seizure-freedom (FAS) was 85.2% with lacosamide versus 88.0% with carbamazepine-CR (PPS: 87.4%; 90.2%) ; 69.1% of lacosamide-treated and 65.1% of carbamazepine-CR-treated patients completed 6-months without seizure. Kaplan-Meier estimated 12-month seizure-freedom (FAS) was 75.7% with lacosamide versus 78.9% with carbamazepine-CR. Overall, 266 (59.9%) lacosamide-treated and 264 (59.7%) carbamazepine-CR-treated patients completed the trial. The most common reasons for premature discontinuation were adverse events (lacosamide: 48 [10.8%]; carbamazepine-CR: 69 [15.6%]), consent withdrawn (46 [10.4%]; 38 [8.6%]), and lack of efficacy (47 [10.6%]; 31 [7.0%]). Conclusions: Lacosamide showed similar efficacy to carbamazepine-CR in patients with newly-diagnosed epilepsy, regardless of their baseline disease severity. Study Supported by: UCB Pharma Disclosure: Dr. Toledo has received personal compensation for activities with UCB Pharma, BIAL, EISAI, Esteve, and Shire as a consultant. Dr. Toledo has received research support from EISAI and BIAL. Dr Baulac received personal compensation for activities with EISAI, UCB, SAGE as a consultant and speaker. Dr Baulac has received research support from EISAI and UCB pharma. Dr. Rosenow has received personal compensation for activities with Sandoz, Hexal, EISAI GmbH, cerbomed, Bayer-Vital UCB Pharma, Desitin GmbH, Shire, and Novartis as a consultant or speaker. Dr. Terada has personal compensation for activities with UCB Pharma, GlaxoSmithKline, and Otsuka Pharmaceutical as a speaker. Dr. Li has received personal compensation for activities with UCB Pharma as an employee. Dr. De Backer has received personal compensation for activities with UCB Pharma as an employee. Dr. Broch has received personal compensation for activities with UCB Pharma as an employee. Dr. Werhahn has received personal compensation for activities with UCB Pharma. Dr. Werhahn holds stock and/or stock options in UCB Pharma.