European Medicines Agency (EMA) Accepts Bial's Submission for Once-daily Epilepsy Treatment Zebinix® (eslicarbazepine acetate) as Monotherapy for Partial-onset Seizures

PORTO, Portugal and HATFIELD, England, May 17, 2016 /PRNewswire/ --

PRESS RELEASE FOR EU MEDIA ONLY: NOT FOR AUSTRIAN/SWISS/US JOURNALISTS 

BIAL announces today that the European Medicines Agency (EMA) has accepted Bial's application to review recent clinical trial data for Zebinix^® (eslicarbazepine acetate) for its use as a once-daily monotherapy in the treatment of adult patients with newly diagnosed partial-onset (focal) epilepsy.

Partial-onset seizures, also known as focal, are the most common type and are therefore an important first target for treatment.^[1] Zebinix^®, (eslicarbazepine acetate) is currently indicated in Europe as an adjunctive therapy in adults with partial-onset seizures, with or without secondary generalisation.^[2] In the US, eslicarbazepine acetate (Aptiom®) is indicated for the treatment of partial-onset seizures as monotherapy or as an adjunctive therapy.^[3]

Commenting on the submission António Portela, CEO of Bial, explains, "It is a significant milestone in Bial's commitment to help people who live with epilepsy. We have been developing eslicarbazepine acetate for many years and it's very encouraging to have the monotherapy submission acceptance. We hope it will become available for those living with epilepsy and for those who manage the condition."

The submission was based on the results from a Bial sponsored Phase III study^[4],[5] in adult patients with newly diagnosed partial-onset seizures which demonstrates that treatment with monotherapy is as effective as controlled-release carbamazepine, a standard of care, and is well-tolerated.

This phase III study^[4],[5] is a randomised, double-blind, parallel-group, active-controlled and non-inferiority study, that investigates the efficacy and safety of once-daily eslicarbazepine acetate (800 to 1600 mg/daily) as monotherapy treatment for newly diagnosed adults (18 years and older) with partial-onset seizures in comparison with twice-daily controlled-release carbamazepine (400 to 1200 mg/daily). The primary endpoint was the proportion of people seizure free for the entire 26-week evaluation period. Secondary endpoints included the time to first seizure, a QOLIE-31 quality of life assessment, and safety. These data were recently presented for the first time at the Academy of Neurology Annual Meeting April 2016.

Efficacy analysis from this study^[4] shows seizure freedom rates of 71% with eslicarbazepine acetate and 75.6% controlled-release carbamazepine in 785 eligible patients at ≥6 months at the last evaluated dose (average risk difference -4.28%, 95%CI -10.3, 1.74%). The one-year seizure-free rate at the last evaluated dose was 64.7% in the eslicarbazepine acetate group and 70.3% in the controlled-release carbamazepine group (average risk difference: -5.46%; 95%CI: -11.88, 0.97%).

A safety analysis^[5] in 813 patients shows that once-daily eslicarbazepine acetate is well tolerated and side effects are mild to moderate. Incidence rates of treatment emergent adverse events (TEAEs) were similar but slightly lower in patients receiving eslicarbazepine acetate versus patients receiving controlled-release carbamazepine (77.8% vs 80.1% respectively). Possibly-related TEAEs for eslicarbazepine acetate were 43.6% compared with 51.5% for controlled release carbamazepine.  Serious treatment-related TEAEs in eslicarbazepine acetate treated patients versus patients treated with controlled release carbamazepine were 2.0% vs 2.7% and for TEAEs leading to withdrawal were 13.5% vs 18%.The most frequently reported possibly-related TEAEs for eslicarbazepine acetate were headache, dizziness, nausea, fatigue, and somnolence.

Eslicarbazepine acetate is a voltage-gated sodium channel blocker. It selectively targets the slow inactivated state of the sodium ion channel^[6] which, stops sodium entering the nerve cells in the brain.^[7] This reduces the activity of the nerve cells, reducing the intensity and the number of seizures.^[7]

Notes to Editors 

About Zebinix (eslicarbazepine acetate)  

Eslicarbazepine acetate is currently marketed in Europe by BIAL-Portela & Cª, S.A and by BIAL´s licensee, Eisai Europe Limited, a European subsidiary of Eisai Co., Ltd. under the trade name Zebinix^®. In the United States and Canada eslicarbazepine acetate (tradename Aptiom®) is marketed by Sunovion Pharmaceuticals Inc., under an exclusive license from BIAL.

• Zebinix is the EU trade name for eslicarbazepine acetate
• Zebinix is under license from BIAL
• Aptiom^® is the trade name for eslicarbazepine acetate in the U.S. and Canada and is under license to Sunovion Pharmaceuticals Inc.

Eslicarbazepine acetate is indicated in Europe as adjunctive therapy in adults with partial onset seizures, with or without secondary generalisation.^[2]

The efficacy of eslicarbazepine acetate was demonstrated in an initial proof-of-concept phase II study^[8] and three subsequent phase III randomised, placebo controlled studies in 1049 patients with refractory partial onset seizures.^{[9],[10],[11]}

Eslicarbazepine acetate is already available in Albania*, Austria, Czech Republic, Cyprus*, Denmark, Finland, France, Germany (co-promotion with BIAL, the developer of eslicarbazepine acetate), Greece, Iceland, Italy, Malta*, Norway, Portugal*, Republic of Ireland, Russia, Scotland, Slovakia, Sweden, Spain (co-promotion with BIAL), UK (co-promotion with BIAL) and the U.S and Canada**.

*Exclusively by BIAL

**Eslicarbazepine acetate is sold in the U.S. and Canada under the trade name Aptiom^®

About BIAL  

Founded in 1924, BIAL is an international pharmaceutical company with the mission to discover, develop and provide therapeutic solutions within the area of health. In recent decades, BIAL has focused on quality, innovation and internationalisation.

Being the partner of choice for many companies, BIAL is strongly committed to therapeutic innovation, investing more than 20% of its turnover in Research and Development (R&D) every year.

BIAL has established an ambitious R&D program centred on the central nervous, cardiovascular system and allergy immunotherapy. BIAL's innovative programmes focus on continuing the clinical development of its anti-epileptic Zebinix/Aptiom (on the market in Europe and the USA), as well as opicapone for Parkinson's disease.

The company expects to introduce more new medicines and vaccines to the market in the next years, strengthening its position worldwide and accomplishing the company's purpose of "Caring for your Health".

For more information about BIAL, please visit http://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 http://www.eisai.com.

References:  

1. European Medicines Agency. Guideline on clinical investigation of medicinal products in the treatment of epileptic disorders 2010 (22 July); CHMP/EWP/566/98 Rev.2/Corr

2. Zebinix® Summary of Product Characteristics http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000988/WC500047225.pdf (accessed April 2015)

3. Food and Drug Administration, Highlights of Prescribing Information https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022416s001lbl.pdf (accessed May 2016)

4. Trinka E, et al. Efficacy of eslicarbazepine acetate versus controlled-release carbamazepine as monotherapy in patients with newly diagnosed partial-onset seizures. Presented at AAN 2016; abstract 001

5. Kowacs P, et al. Safety and tolerability of eslicarbazepine acetate as monotherapy in patients with newly diagnosed partial-onset seizures. Presented at AAN 2016; abstract 002

6. 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

7. European Medicines Agency, Zebinix eslicarbazepine acetate, How does it work? http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000988/human_med_001172.jsp&mid=WC0b01ac058001d124 (accessed April 2016)

8. 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

9. 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

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

11. 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 Neurol Scand. 2009; 120:281-7

Date of preparation: May 2016

Job code: Zebinix-UK 2402