Abstracts

Rationale: Eslicarbazepine acetate (ESL) is a once-daily (QD) antiepileptic drug (AED), approved by EMA and FDA as treatment of focal (partial-onset) seizures. Approval of ESL by EMA as monotherapy for newly diagnosed adults with focal seizures considered a Phase III, randomized, double-blind, active-controlled, non-inferiority study (Study 311).1 Methods: Patients who completed the double-blind Phase III trial, and remained seizure free for ≥6 months at the last evaluated dose, were eligible to enter a 2-year open-label extension (OLE) study (311-EXT), in which all patients received open-label treatment with flexibly-dosed ESL monotherapy (Figure 1).Patients who required concomitant AED treatment (a total of 22/206 [10.7%]) during the OLE study were excluded from the analysis presented here.Efficacy assessments included seizure freedom rate and overall treatment satisfaction.Safety assessment included TEAEs, treatment-related TEAEs, serious TEAEs, TEAEs by severity, and TEAEs leading to discontinuation. Results: A total of 206 patients entered the OLE study (ESL/ESL, n=109; CBZ-CR/ESL, n=97). Demographic and baseline characteristics of patients in the ESL/ESL and CBZ-CR/ESL groups were generally similar. Overall, 155/184 (84.2%) patients completed the study and completion rates were similar between groups (ESL/ESL, 83.3%; CBZ-CR/ESL, 85.2%).The majority of patients, 184 out of 206 (89.3%), remained under ESL monotherapy throughout the OLE study (ESL/ESL, n=96 ; CBZ-CR/ESL, n=88), and maintained the same ESL dose during the OLE study (ESL/ESL, 95.8%; CBZ/ESL, 89.8%).158/184 (85.9%) of patients maintained seizure freedom during the 2-year OLE study. At the end of study visit, overall treatment satisfaction was rated as ‘very good’ or ‘good’ by 100% of patients and investigators.Overall, 109/184 (59.2%) patients reported TEAEs (ESL/ESL, 53.1%; CBZ-CR/ESL, 65.9%) (Table 1). TEAEs considered to be at least possibly related to treatment were reported for 33/184 (17.9%) patients overall, and rates were similar for the ESL/ESL (17.7%) and CBZ-CR/ESL (18.2%) groups. The majority of TEAEs were of mild or moderate intensity (77.7% overall; ESL/ESL, 69.8%; CBZ-CR/ESL, 86.4%). Serious TEAEs were reported for 12/184 (6.5%) patients overall (ESL/ESL, 7.3%; CBZ-CR/ESL, 5.7%). No serious TEAE was reported for more than one patient. Withdrawal due to treatment-emergent adverse events was low and similar between groups (ESL/ESL, 3.1%; CBZ-CR/ESL, 4.5%).From OL baseline (OLB) to EOS, high GGT decreased in CBZ-CR/ESL (49.5% to 16.3%) and increased in ESL/ESL (21.9% to 28.2%). High total cholesterol decreased in CBZ-CR/ESL and ESL/ESL from 32.6% to 17.5% and from 19.0% to 12.8%, respectively. Conclusions: Efficacy of ESL monotherapy observed in the double-blind Phase III trial was largely sustained during this 2-year OLE study in patients initially treated with ESL monotherapy and in those who transitioned from CBZ-CR monotherapy.The long-term safety/tolerability of ESL monotherapy was consistent with what has been reported in previous clinical trials including OLE studies1 and no new safety signals emerged. These findings support the use of ESL as long-term monotherapy in newly diagnosed patients with focal epilepsy, including in those patients previously treated with CBZ-CR.References1.Trinka E et al. Efficacy and safety of eslicarbazepine acetate versus carbamazepine monotherapy in newly diagnosed epilepsy.Epilepsia 2018;59:479–91. 2.Zebinix® Summary of Product Characteristics 2018. Funding: No funding