Zebinix® (eslicarbazepine acetate) Data Demonstrate No Significant Negative Consequences on Neurocognitive Function in Children with Focal Epilepsy

PORTO, Portugal and HATFIELD, England, June 23, 2017 /PRNewswire/ --

FOR EMEA MEDIA ONLY - NOT FOR SWISS/AUSTRIAN JOURNALISTS    

• 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 tolerated^[2]   
• Study 208 data presented at the 12th European Paediatric Neurology Society (EPNS) Congress in Lyon, France    

Bial and Eisai today 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 will be presented today 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 eslicarbazepine acetate 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.^[8] 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]

The continued development of eslicarbazepine acetate underscores Bial's and Eisai's commitment to developing and delivering highly beneficial new treatments to help improve the lives of people with epilepsy.

Notes to Editors   

About Epilepsy    

Epilepsy is one of the most common neurological conditions in the world, affecting approximately 6 million people in Europe, and an estimated 50 million people worldwide.^[9] Epilepsy is a chronic disorder of the brain that affects people of all ages. It is characterised by abnormal discharges of neuronal activity, which causes seizures. Seizures can vary in severity, from brief lapses of attention or jerking of muscles, to severe and prolonged convulsions. Depending on the seizure type, seizures may be limited to one part of the body, or may involve the whole body. Seizures can also vary in frequency from less than one per year, to several per day. Epilepsy has many possible causes but often the cause is unknown.

About Study 208^[1]

Study 208 was a Phase II, randomised, double-blind, placebo-controlled study (part I) followed by a one-year open-label, uncontrolled period (part II), aimed to evaluate the effect of eslicarbazepine acetate on cognition in children 6-16 years with focal seizures.

Part I consisted of a four week observational baseline period, a 12 week double-blind period (four-week up-titration and eight week maintenance) and tapering-off periods (4-8 weeks of down-titration and follow-up).

In part II patients received ten mg/kg/day of eslicarbazepine acetate, which could be titrated up to 30 mg/kg/day according to clinical response (maximum 1.200 mg once-daily).

About Zebinix^® (eslicarbazepine acetate)

Eslicarbazepine acetate is a voltage-gated sodium channel blocker which selectively targets the slow inactivated state of the sodium ion channel.^[10] Further, eslicarbazepine acetate does not inhibit potassium efflux, which may reduce the potential for repetitive neuronal firings.^[10] The efficacy of eslicarbazepine acetate was demonstrated in an initial proof-of-concept Phase II study^[11] and three subsequent Phase III randomised, placebo controlled studies in 1,049 people with refractory partial onset seizures.^{[12],[13],[14]}

Eslicarbazepine acetate is currently marketed in Europe and Russia by Bial and by Bial's licensee, Eisai Europe Limited, a European subsidiary of Eisai Co Ltd under the trade name Zebinix^® or Exalief^®. In the United States and Canada eslicarbazepine acetate (tradename Aptiom^®) is marketed by Sunovion Pharmaceuticals Inc under an exclusive license from Bial.

About Bial    

Founded in 1924, Bial's mission is to discover, develop and provide therapeutic solutions within the area of health. In recent decades, Bial has strategically focused on quality, innovation and internationalisation.

Bial is strongly committed to therapeutic innovation, investing more than 20 per cent of its turnover in Research and Development (R&D) every year.

Bial has established an ambitious R&D program centered on the neurosciences and cardiovascular system. The company expects to introduce more new medicines to the market in the next years, strengthening its international presence based in its own innovative medicines and accomplishing the company's purpose of "Caring for your Health."

For more information about Bial, please visit www.bial.com

About Eisai Co Ltd    

Eisai Co Ltd. is a leading global research and development-based pharmaceutical company headquartered in Japan. We define our corporate mission as "giving first thought to patients and their families and to increasing the benefits health care provides," which we call our human health care (hhc) philosophy. With over 10,000 employees working across our global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realise our hhc philosophy by delivering innovative products in multiple therapeutic areas with high unmet medical needs, including Oncology and Neurology. 

As a global pharmaceutical company, our mission extends to patients around the world through our investment and participation in partnership-based initiatives to improve access to medicines in developing and emerging countries.

For more information about Eisai Co., Ltd., please visit www.eisai.com        

References   

1. Veggiotti P, et al. Effect of eslicarbazepine acetate on neurocognitive functions in children with epilepsy. Presented at EPNS 2017. Oral Presentation #OC58 

2. 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 

3. Mula M, et al. Antiepileptic Drug-Induced Cognitive Adverse Effects. CNS Drugs 2009;23:121-137 

4. Guerrini R. Epilepsy in Children. The Lancet 2006;9505:499-524. 

5. Melbourne Chambers R, et al. Cognition, academic achievement and epilepsy. Epilepsy & Behavior 2014;39-44 

6. Mitchell WG, et al. Academic underachievement in children with epilepsy. Journal of Child Neurology 1991;6:65-72. 

7. Carpay HA, et al. Disability due to restrictions in childhood epilepsy. Developments in Medicine & Child Neurology 1997;39:521-6. 

8. Zebinix^® (eslicarbazepine acetate) Summary of Product Characteristics. Available at: www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000988/WC500047225.pdf Accessed June 2017.  

9. Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe. Available at: www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf Accessed June 2017 

10. 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 

11. 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 

12. 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 

13. Ben-Menachem E, et al. Eslicarbazepine acetate as adjunctive therapy in adult patients with partial epilepsy. Epilepsy Research 2010;89(2-3):278-85 

14. 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

June 2017 
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