All Wales Strategic Medical Group Approves Zebinix® (Eslicarbazepine Acetate) - Once Daily Anti-Epileptic Treatment

HATFIELD, England, November 22, 2012 /PRNewswire/ --

The All Wales Strategic Medical Group (AWSMG) has approved Zebinix^® (eslicarbazepine acetate) for the treatment of partial seizures in highly refractory patients who remain uncontrolled with, or are intolerant to, other anti-epileptic medicine combinations. Eslicarbazepine acetate is licenced in Europe as an adjunctive therapy for adults with partial-onset seizures with or without secondary generalisation.^[1]

"There are 32,000 people in Wales living with epilepsy. Epilepsy is a complex condition which can be very difficult to treat. Up to 70 per cent of people with epilepsy could have their seizures controlled but only 52 per cent actually do. We welcome the decision by the AWSMG to make Zebinix available as an add-on treatment for people with difficult to control epilepsy who could benefit from this epilepsy medicine," commented Ann Sivapatham, Epilepsy Action's Wales Manager.

Epilepsy affects nearly 32,000 people in Wales.^[2] The successful treatment of partial-onset seizures (the most common form of epilepsy) remains a significant challenge in some patients and the incidence of uncontrolled partial epilepsy remains high, between 20 - 40% of patients with epilepsy have remained poorly controlled despite these treatments, despite many existing anti-epileptic drugs (AEDs).^[3]

Nick Burgin, Director Market Access, Eisai EMEA & Russia explained: "We are delighted that AWSMG has approved Zebinix for partial epilepsy. We want to ensure that patients have access to innovative treatments, encouraging better patient outcomes and faster uptake of new medicines."

Zebinix was approved by the European Commission following data which showed that it reduces seizure frequency and has an overall positive efficacy and safety profile.Zebinix is already available in Albania*, Austria, Czech Republic, Cyprus*, Denmark, England, Finland, France, Germany, Greece, Iceland, Malta*, Norway, Portugal*, Republic of Ireland, Scotland, Sweden, Spain (co-promotion with BIAL, the developer of Zebinix) and Wales.

Notes to Editors

Zebinix^® is the EU trade name for eslicarbazepine acetate

Zebinix^® is under license from BIAL except in those countries marked with an asterix, where it is exclusively by Bial

About epilepsy, partial-onset seizures and their treatment

Epilepsy is a chronic neurological disease characterised by abnormal discharges of neuronal activity causing seizures. Depending on the seizure type, seizures may be limited to one part of the body, or may be generalised to involve the whole body. Patients may also experience abnormal sensations, altered behaviour or altered consciousness. Epilepsy is a disorder with many possible causes. Often the cause of epilepsy is unknown. However, anything that disturbs the normal pattern of neuron activity - from illness to brain damage to tumours, can lead to seizures.^[4]

Epilepsy is characterised by abnormal firing of impulses from nerve cells in the brain. In partial-onset seizures, these bursts of electrical activity are initially focused in specific areas of the brain,^[5] but may become more generalised, the symptoms vary according to the affected areas.^[6]

Epilepsy is one of the world's most common neurological disorders, affecting more than six million people across Europe.^[7] With significant health care costs and economic impacts,^[8] uncontrolled seizures also increase the risk of psychological comorbidities, such as anxiety and depression.^[9]

About Zebinix^®(eslicarbazepine acetate)

Eslicarbazepine acetate is a voltage-gated sodium channel blocker.^[10] It preferably targets the inactivated state of the sodium ion channel, preventing its return to the active state, and thereby reduces repetitive neuronal firing.^[10] Recent studies have also demonstrated that eslicarbazepine acetate effectively inhibits voltage-gated calcium channels, therefore enhancing its potential as an anti-epileptic agent.^[11] The efficacy of eslicarbazepine acetate was demonstrated in an initial proof-of-concept phase II study^[12] and three subsequent phase III randomised, placebo controlled studies in 1049 patients with refractory partial onset seizures.^{[13],[14],[15]}

Clinical data

The EU approval was based on data from a phase II and three phase III clinical trials.^[9,10,11,12] Patients recruited in the phase III trials had a history of at least four partial seizures per month despite treatment between one to three  concomitant anti-epileptic drugs.^{[10],[11],[12]}

During the trials, patients were randomised to various dosages of Zebinix^® or placebo and after a 2-week titration period, were assessed over a 12-week maintenance period, with continued follow-up over a one year open-label period.^{[10,11,12,16,17,18]}

Efficacy

Over the 12-week maintenance period, Zebinix^® 800mg and 1200mg once-daily significantly reduced seizure frequency, and was significantly more effective than placebo.^[9,10,11,12] Long-term safety and maintenance of therapeutic effect was demonstrated in one-year open-label extensions of these studies.^[13,14,15]

Tolerability^[9,10,11,12]

In the Phase III clinical trials adverse events mainly occurred during the first 6 weeks of treatment and the majority of patients experienced adverse events of mild to moderate intensity. After the initial 6 weeks of treatment there were no observed differences in the incidence of side effects between patients treated with Zebinix^® and the placebo group. The most common treatment-emergent adverse events in the pivotal studies were dizziness, headache and somnolence.

License Agreement

Eisai Europe Limited,a European subsidiary of Eisai Co., Ltd. announced in February 2009 that it had entered into a license and co-promotion agreement with BIAL - Portela & Cª, S.A. (Headquarters: São. Mamede do Coronado, Portugal, "BIAL"), which gave Eisai Europe Limited rights to sell BIAL's anti-epileptic drug Zebinix^®(eslicarbazepine acetate) in Europe.

About Eisai EMEA in Epilepsy:

Eisai is committed to developing and delivering highly beneficial new treatments to help improve the lives of people with epilepsy. The development of AEDs is a major strategic area for Eisai in Europe, the Middle East, Africa and Russia (EMEA).

In the EMEA region, Eisai currently has four marketed treatments including:

• Zonegran^® (zonisamide) as monotherapy and adjunctive therapy in adult patients with partial-onset seizures, with or without secondary generalisation. (Zonegran is under license from the originator Dainippon Sumitomo Pharma)
• Zebinix^® (eslicarbazepine acetate) as adjunctive therapy in adult patients with partial-onset seizures, with or without secondary generalisation. (Zebinix is under license from BIAL)
• Inovelon^® (rufinamide) for the adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome in patients >4 years
• Fycompa^® (perampanel) for use as an adjunctive treatment for partial onset seizures, with or without secondarily generalised seizures, in patients with epilepsy aged 12 years and older

About Eisai:

Eisai recently expanded their UK Hatfield commercial, research and manufacturing facility which now supports the company's growing EMEA business.

Eisai concentrates its R&D activities in three key areas:

• Neuroscience, including: Alzheimer's disease, epilepsy, pain and weight loss
• Oncology including: anticancer therapies; tumour regression, tumour suppression, antibodies, etc
• Vascular/Immunological reaction including: thrombocytopenia, rheumatoid arthritis, psoriasis, inflammatory bowel disease

With operations in the U.S., Asia, Europe and its domestic home market of Japan, Eisai employs more than 11,000 people worldwide. In Europe, Eisai undertakes sales and marketing operations in over 20 markets, including the United Kingdom, France, Germany, Italy, Spain, Switzerland, Sweden, Ireland, Austria, Denmark, Finland, Norway, Portugal, Iceland, Czech Republic, Slovakia, the Netherlands, Belgium, Luxembourg, the Middle East and Russia.

For further information please visit our web site http://www.eisai.com.

About BIAL

Founded in 1924, BIAL is an international pharmaceutical group with products available in more than 50 countries throughout four continents. BIAL is a privately held Portuguese research based pharmaceutical company and the largest Portuguese pharmaceutical company, based in S. Mamede do Coronado, Portugal, responsible for the research and development of eslicarbazepine acetate (Zebinix^®).

It is the partner of choice for many pharma companies, having a strong presence in the Iberian Peninsula as well as in over 10 countries in Latin America and in around 20 French or Portuguese speaking African countries.

BIAL is strongly committed to therapeutic innovation investing more than 20% of its turnover in research and development every year. Key research areas for BIAL are the central nervous system, the cardiovascular system and allergen immunotherapy. BIAL currently has several other innovative programs under development, which the company expects to bring to the market within the next years, thereby strengthening its position throughout Europe.

Further information about BIAL can be found at http://www.bial.com

References

1. AWSMG advice on Zebinix available at: http://www.wales.nhs.uk/sites3/Documents/371/Eslicarbazepine%20%28Zebinix%29%20FAR.pdf  [http://www.wales.nhs.uk/sites3/Documents/371/Eslicarbazepine %28Zebinix%29 FAR.pdf ]

2. Joint Epilepsy Council. http://www.jointepilepsycouncil.org.uk/downloads/2011/Joint%20Epilepsy%20Council%20Prevalence%20and%20Incidence%20September%2011.pdf [http://www.jointepilepsycouncil.org.uk/downloads/2011/Joint Epilepsy Council Prevalence and Incidence September 11.pdf ]  

3. French JA. Refractory Epilepsy; Clinical Overview. Epilepsia 2007: 48 (Suppl1) 3 - 7

4. Epilepsy Research UK. What is Epilepsy? Fact sheet.: http://www.epilepsyresearch.org.uk/about_us/leaflets/lflt1.htm (accessed March 2012)

5. Epilepsy Action. Describing Seizure Types.  http://www.epilepsy.org.uk/info/seizures/ataglance (Accessed March 2012)

6. NHS Choices. Symptoms of Epilepsy.  http://www.nhs.uk/Conditions/Epilepsy/Pages/Symptoms.aspx (Accessed March 2012)

7. The Lancet Neurology. 2010 Oct; 9(10): 941

8. Pugliatti M et al. Epilepsia 2007: 48(12) 2224 - 2233.

9. Titlic, M. Basic, S. Hajnek, S. Bratisl Lek Listy (Bratislava Medical Journal) 2009; 110 (2): 105 - 109

10. Almeida L, Soares-da-Silva P. Eslicarbazepine acetate (BIA 2-093). Neurotherapeutics. 2007 Jan;4(1):88-96

11. Brady K et al. Abstract presented at International Epilepsy Congress 2011 p858.

12. Elger et al. Epilepsia, 48(3):497-504, 2007

13. Elger C, Halász P, Maia J et al. Epilepsia 2009; 50(3):454-463

14. Ben-Menachem E, Gabbai A, Hufnagel A, Maia J, Almeida L, Soares-da-Silver P. Epilepsy Research 2010;89:278-285.

15. Gil-Nagel A, Lopes-Lima J, Maia J et al. Acta Neurol Scand 2009: 120: 281-287

16. Halász P, Elger C, Guekht A, et al. Epilepsia, 51(10):1963-1969, 2010

17. Gabbai A, Ben-Menachem E, Maia J, et al. Epilepsia. 2008;49(Suppl. 7):432-3

18. Lopes-Lima J, Gil-Nagel A, Maia J, et al. Epilepsia. 2008;49(Suppl. 7):441-2.

 

Date of preparation: November 2012

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