Zebinix® (eslicarbazepine acetate) Data Demonstrate No Significant Negative Consequences on Neurocognitive Function in Children with Focal Epilepsy
Posted in Industry News on 28th Jun 2017
Eslicarbazepine acetate was shown not to have a significant negative consequence on attention, information processing and working memory; 1 in addition it was shown to be efficacious and generally well tolerated2
Study 208 data presented at the 12th European Paediatric Neurology Society (EPNS) Congress in Lyon, France
22nd June: Bial and Eisai announced data from a Phase II study which showed that treatment with Zebinix® (eslicarbazepine acetate) had no significant negative impact on attention, information processing and working memory in children aged 6-16 years old with focal-onset epilepsy.1 It is well-documented that some anti-epileptic drugs (AEDs) may contribute to negative effects on cognition in epilepsy, underscoring the importance of this clinically meaningful data.3
Data was presented 22nd June in an oral presentation at the EPNS Congress in Lyon, France.1
Study 208 is a randomised Phase II trial evaluating the effect of adjunctive eslicarbazepine acetate (n=83) on Power of Attention in children aged 6-16 years old with refractory focal onset epilepsy versus placebo (n=40). Eslicarbazepine acetate also demonstrated no statistically significant difference for secondary endpoints including continuity of attention, quality of working memory and speed of memory at the end of Part I.1
“Childhood and adolescence are critical times for learning and development,” explains Ann Connolly, Registered Advanced Nurse Practitioner Epilepsy (Childhood), National Children’s Hospital, Adelaide and Meath Hospital, Dublin, Ireland. “These findings may indicate that eslicarbazepine acetate has no significant negative consequence on the neurocognitive capability of children. This is important as the treatment may help support normal learning and schooling, which will stand these children in good stead for the future.”
For the overall age group there were no significant Power of Attention differences in Part I between eslicarbazepine acetate and placebo, with a Least Square mean difference of 33.2 milliseconds (95% CI: – 137.6, 204.0; p=0.700). Power of Attention was defined as the sum of the reaction time measures from the attentional tasks (simple reaction time [dominant hand only], choice reaction time and digit vigilance speed.1 Overall incidence in study 208 of treatment emergent adverse events (TEAEs) was similar (45% for ESL and 48% for placebo).2 The most frequently reported TEAEs with eslicarbazepine acetate treatment were headache, somnolence and vomiting.2
“A major treatment goal for neurologists managing childhood epilepsy is to achieve seizure freedom with minimal or no adverse effects, of which neurocognition is an important consideration. Few clinical trials have examined the cognitive effects of AEDs in childhood epilepsy so this new data is reassuring and supports the use of eslicarbazepine acetate in these difficult-to-treat patients,” commented Professor Stéphane Auvin, Professor of Epilepsy & Child Neurology at the Université Denis Diderot, member of the Paediatric Commission of ILAE and board member of the French Paediatric Neurology Society Paris, France.
Approximately 10.5m children and adolescents worldwide are estimated to have active epilepsy.4 Children with epilepsy may suffer from cognitive impairment and have impaired ability to learn.5 Epilepsy may have a significant impact on a child’s quality of life, academic achievement and psychosocial outcomes in later life.6, 7
Eslicarbazepine acetate is indicated in Europe as adjunctive therapy in adults, adolescents and children aged above 6 years, with partial-onset seizures with or without secondary generalisation.[viii] Eslicarbazepine acetate is also indicated in Europe as a monotherapy in the treatment of partial-onset seizures, with or without secondary generalisation, in adults with newly diagnosed epilepsy.8
[i] Veggiotti P, et al. Effect of eslicarbazepine acetate on neurocognitive functions in children with epilepsy. Presented at EPNS 2017. Oral Presentation #OC58
[ii] Jóźwiak S, et al. Efficacy and tolerability of eslicarbazepine acetate in children with epilepsy: results from a phase II study. Presented at EPNS 2017. Oral Presentation #OC57
[iii] Mula M, et al. Antiepileptic Drug-Induced Cognitive Adverse Effects. CNS Drugs 2009;23:121-137
[iv] Guerrini R, Epilepsy in Children, The Lancet 2006; 9505:499-524.
[v] Melbourne Chambers R, et al. Cognition, academic achievement and epilepsy. Epilepsy & Behavior 2014; 39-44
[vi] Mitchell WG, et al. Academic underachievement in children with epilepsy. Journal of Child Neurology 1991;6:65–72.
[vii] Carpay HA, et al. Disability due to restrictions in childhood epilepsy. Developments in Medicine & Child Neurology 1997;39:521–6.
[viii] Zebinix® (eslicarbazepine acetate) Summary of Product Characteristics. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000988/WC500047225.pdf Accessed June 2017.
[ix]Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe. Available at: http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf Accessed June 2017
[x] Hebeisen S, et al. Eslicarbazepine and the enhancement of slow inactivation of voltage-gated sodium channels: a comparison with carbamazepine, oxcarbazepine and lacosamide. Neuropharmacology 2015; 89:122-35
[xi] Elger C, et al. Eslicarbazepine acetate: A double-blind, add-on, placebo-controlled exploratory trial in adult patients with partial-onset seizures. Epilepsia 2007; 48:497-504
[xii]Elger C, et al. Efficacy and safety of eslicarbazepine acetate as adjunctive treatment in adults with refractory partial-onset seizures: A randomised, double-blind, placebo-controlled, parallel-group phase III study. Epilepsia 2009;50:454-63
[xiii]Ben-Menachem E, et al. Eslicarbazepine acetate as adjunctive therapy in adult patients with partial epilepsy. Epilepsy Research 2010;89(2-3):278-85
[xiv]Gil-Nagel A, et al. Efficacy and safety of 800 and 1200 mg eslicarbazepine acetate as adjunctive treatment in adults with refractory partial-onset seizures. Acta Neurologica Scandinavica 2009; 120:281-87