LONDON, November 8, 2010 /PRNewswire/ -- Zebinix(R) (eslicarbazepine acetate), a treatment for epilepsy, has been accepted for restricted use in Scotland after a decision by The Scottish Medicines Consortium (SMC).[1] Following the new clinical and cost effectiveness decision, Zebinix can now be used as an add-on (adjunctive) therapy in adults with partial-onset seizures, with or without secondary generalisation (where the seizure spreads to both sides of the brain). The Committee adds that Zebinix use should be restricted to patients with hard-to-treat (highly refractory) epilepsy who have been heavily pre-treated and remain uncontrolled with existing anti-epileptic drugs, contingent upon the continuing availability of the patient access scheme in Scotland.

Epilepsy is one of the most common neurological diseases, affecting nearly 40,000 people in Scotland[2] - and the successful treatment of partial-onset seizures (the most common type of epilepsy) remains a challenge. Up to 40% of patients with partial seizures do not achieve seizure control with current treatments.[3]

Being able to adequately control seizures is a continual challenge for doctors looking after people with epilepsy. Uncontrolled seizures place a huge burden on patients and their families and are associated with poor quality of life, reduced likelihood of employment and an increased risk of psychological comorbodities such as depression and anxiety. Today's recommendation by the SMC to make Zebinix available in Scotland is a very welcome decision - it gives physicians another string to their therapeutic bow and people with epilepsy the possibility of improved seizure control, commented Martin Brodie, Professor of Medicine and Clinical Pharmacology at the University of Glasgow and Director, Epilepsy Unit, Western Infirmary, Glasgow.

Zebinix was approved for use by the European Medicines Agency in April 2009 for the treatment of adults with partial-onset seizures with or without secondary generalisation.[4] In its first year Zebinix has had over 9,000 months of patient exposure.[5]

Notes to Editors

Zebinix(R) is the EU trade name for eslicarbazepine acetate.

Zebinix(R) is under license from Bial.

About epilepsy, partial-onset seizures and their treatment

Epilepsy is one of the most common neurological diseases, affecting approximately 1 in 130 people in the UK.[6]

Epilepsy is a chronic neurological disease characterised by abnormal discharges of neuronal activity causing seizures. Clinically, these manifest as convulsions or jerking of muscles. 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 abnormal brain development, can lead to seizures.

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, but may become more generalised; the symptoms vary according to the affected areas. Nerve impulses are triggered via voltage-gated sodium channels in the nerve cell membrane.

Treatment of partial-onset seizures, the most common type of epilepsy, presents a constant challenge - up to 40% of patients with partial-onset seizures do not achieve seizure control with current anti-epileptic drugs.3

Furthermore, adverse events, such as lightheadedness (dizziness), somnolence (sleepiness), and cognitive slowing, are highly prevalent with existing anti-epileptic agents. Hence, there is a need for new anti-epileptic agents that offer effective reduction in seizure frequency combined with a favourable safety profile.

About Zebinix (eslicarbazepine acetate)

Zebinix is indicated as adjunctive therapy in adults with partial-onset seizures with or without secondary generalisation.4 Zebinix is a novel, once-daily, voltage-gated sodium channel blocker.[7],[8] It specifically targets the inactivated state of the ion channel, preventing its return to the active state, and thereby reduces repetitive neuronal firing.8,9 The efficacy of Zebinix has been demonstrated in three randomised, placebo controlled studies in 1049 patients with refractory partial onset seizures.8,[9],[10] Zebinix also significantly improved patient's health related quality of life (HRQoL) as measured by the QOLIE-31 score during a one year open label extension of the above three studies.[11],[12],[13],[14],[15] Zebinix is given orally once-daily.

Clinical data

The EU approval was based on data from phase II and three phase III clinical trials. Patients had a history of at least four partial seizures per month despite treatment with up to three concomitant anti-epileptic drugs.

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.

Efficacy

Over the 12-week maintenance period, Zebinix 800mg and 1200mg once-daily significantly reduced seizure frequency, and was significantly more effective than placebo.[8,10,11,16] This significant decrease in seizure frequency was sustained over the one-year open label treatment period and was consistent regardless of baseline therapy.[17],[18],[19]

Tolerability[8,10,11,17]

In the Phase II and 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 6 weeks of treatment, there were no observed differences in the incidence of side effects between patients treated with Zebinix and the placebo group. Treatment-emergent adverse events affecting 10% of patients in the pivotal studies were dizziness, headache and somnolence.

Quality of life and depressive symptoms[12,13,14,15,16]

The effect of Zebinix on quality of life was assessed using the Quality of Life Epilepsy Inventory-31 (QOLIE-31) scale. There was a statistically and clinically significant improvement from baseline during long-term open-label therapy, including a mean relative improvement in overall quality of life (p0.001 - p0.01 across the three studies) and improvements in individual elements of the QOLIE-31 scale including seizure worry, emotional wellbeing, energy/fatigue, medication effects and social function.

Improvement in depressive symptoms was also measured using the Montgomery Asberg Depression Rating Scale (MADRS). During long-term, open-label therapy, Zebinix demonstrated a statistically significant improvement from baseline in the overall MADRS score (p0.0001) and individual domains of the MADRS scale including pessimistic thoughts, concentration difficulties, apparent sadness and inner tension.

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 C(a), S.A. (Headquarters: São. Mamede do Coronado, Portugal, CEO: Luís Portela, Bial), which gave Eisai Europe Limited rights to sell Bial's anti-epileptic drug Zebinix(R) (eslicarbazepine acetate) in Europe.

About Eisai

Eisai is one of the world's leading RD-based pharmaceutical companies, that has defined its corporate mission as giving first thought to patients and their families and to increasing the benefits health care provides, which we call human health care (hhc).

Eisai concentrates its RD activities in three key areas:

- Integrative Neuroscience: Alzheimer's disease, multiple sclerosis, neuropathic pain, epilepsy, depression, etc - Integrative Oncology: Anticancer therapies; tumour regression, tumour suppression, antibodies, etc and Supportive cancer therapies; pain relief, nausea, etc - Vascular/Immunological Reaction: Acute coronary syndrome, atherothrombotic disease, sepsis, rheumatoid arthritis, psoriasis, Crohn's disease, etc

With operations in the U.S., Asia, Europe and its domestic home market of Japan, we employ more than 10,000 people worldwide, and reported consolidated sales of over GBP3.53 billion in FY2007, an increase of 8.9% year on year. 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, Hungary, and Slovakia.

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

About Bial

Founded in 1924, Bial is an international pharmaceutical group with products available in more than 40 countries throughout four continents. Bail is 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 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 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] Scottish Medical Consortium advice on Zebinix available at: http://www.scottishmedicines.org.uk/Home

[2] Epilepsy Scotland available at: http://www.epilepsyscotland.org.uk/ (Accessed 01 November 2010).

[3] Kwan P, Brodie MJ Early identification of refractory epilepsy. New England Journal of Medicine 2000; 342: 314-9.

[4] European Medicines Agency. Zebinix (eslicarbazepine acetate): summary of product characteristics. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_... (Accessed 2 November 2010)

(Due to the length of this URL, it may be necessary to copy and paste this hyperlink into your Internet browser's URL address field. Remove the space if one exists.)

[5] Eisai Europe Ltd. Data on file.

[6] What is epilepsy? The National Society for Epilepsy. Available from URL: http://www.epilepsysociety.org.uk/AboutEpilepsy/Whatisepilepsy (Accessed 2 November 2010)

[7] Elger C, Halász P, Maia J et al. Efficacy and safety of eslicarbazepine acetate as adjunctive treatment in adults with refractory partial-onset seizures: A randomized, double-blind, placebo-controlled, parallel-group phase III study. Epilepsia 2009; 50(3):454-463.

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

[9] Ben-Menachem E, Gabbai A, Hufnagel A, Maia J, Almeida L, Soares-da-Silver P. Eslicarbazepine acetate as adjunctive therapy in adult patients with partial epilepsy; Epilepsy Research 2010;89:278-285.

[10] Lopes-Lima J, Gil-Nagel A, Maia J et al. Efficacy and safety of eslicarbazepine acetate as add-on treatment in adults with refractory partial-onset seizures: BIA-2093-303 Study. Poster presented at the 8th European Congress on Epileptology, 21-25 September 2008, Berlin, Germany.

[11] Cramer J, Elger C, Halász P et al. Improvement in quality-of-life and depressive symptoms during long term treatment with eslicarbazepine acetate: BIA-2093-301 study (Abstract No. 3.197). Epilepsia. 2008;49(Suppl. 7):426-7.

[12] Soares-da-Silva P, Martins-da-Silva A, Gabbai AA et al. Improvement in quality-of-life and depressive symptoms during long-term treatment with eslicarbazepine acetate: BIA-2093-302 study (Abstract No. 3.254). Epilepsia. 2008;49(7):455-6.

[13] Pereira H, Lopes-Lima J, Gil-Nagel A et al. Improvement in quality-of-life and depressive symptoms during long-term treatment with eslicarbazepine acetate: BIA-2093-303 study (Abstract No. 3.240). Epilepsia. 2008;49(Suppl. 7):446-8.

[14] Cramer J, Maia J, Almeida L, et al. Quality-of-life improvement during long-term treatment with eslicarbazepine acetate (Abs tract No. T278). Epilepsia. 2009;50(Suppl. 4):124.

[15] Hodoba D, Czlonkowska A, Cramer J, et al. Depressive symptoms improvement during long-term treatment with eslicarbazepine acetate (Abstract No. T286). Epilepsia. 2009;50(Suppl. 4):126.

[16] Elger C, French J, Halasz P. et al. Evaluation of Eslicarbazepine Acetate as Add-On Treatment in Patients with Partial-Onset Seizures: Pooled Analysis of Three Double-Blind Phase III Clinical Studies. (Abstract No. 3.199). Epilepsia. 2008;49(Suppl. 7):428-9.

[17] Halász P, Elger C, Guekht A, et al. Long-term-treatment of partial epilepsy with eslicarbazepine acetate (ESL): results of a one-year open-label extension to study BIA-2093- 301 (Abstract No. 3.213). Epilepsia. 2008;49(Suppl. 7):435-6.

[18] Lopes-Lima J, Gil-Nagel A, Maia J, et al. Long-term treatment of partial epilepsy with eslicarbazepine acetate (ESL): results of a one-year open-label extension of study BIA-2093-303 (Abstract No. 3.227). Epilepsia. 2008;49(Suppl. 7):441-2.

[19] Gabbai A, Ben-Menachem E, Maia J, et al. Long-term treatment of partial epilepsy with eslicarbazepine acetate (ESL): results of a one-year open-label extension of study BIA-2093- 302 (Abstract No. 3.208). Epilepsia. 2008;49(Suppl. 7):432-3.

SOURCE: Eisai Europe Limited

CONTACT: For further information please contact: Benjamyn Tan / HelenSwift, Tonic Life Communications, +44(0)20-7798-9923 / +44(0)20-7798-9924,benjamyn.tan@toniclc.com / helen.swift@toniclc.com, Eisai Europe Ltd -Cressida Robson: +44(0)845-676-5318