Once-Daily Epilepsy Treatment now Available in Sweden

HATFIELD, England, May 23, 2012 /PRNewswire/ --



Reimbursement granted for Zebinix^® (eslicarbazepine acetate) as adjunctive therapy for adults with partial-onset seizures

Eisai Europe Limited today announces the launch of Zebinix^® (eslicarbazepine acetate) which will receive full reimbursement from the Swedish health authorities.  

Once-daily Zebinix is indicated as an adjunctive (add-on) therapy for adults with partial-onset seizures, with or without secondary generalisation.[1]

"Up to a third of epilepsy patients do not achieve adequate seizure control after their first anti-epileptic treatment, there is therefore a key medical need for effective adjunctive therapeutic options for epilepsy patients. Zebinix will provide clinicians in Sweden with an important additional treatment option to help patients with uncontrollable seizures manage their condition", [2] said Professor Elinor Ben-Menachem, Department of Clinical Neuroscience and Physiology Sahlgrenska Academy University of Göteborg, Sweden.

Epilepsy is one of the world's most common neurological disorders. The disease affects more than six million people across Europe,[3] and at least 60,000 people in Sweden.[4] The total health care costs and productivity losses due to epilepsy in Sweden is estimated at €441million, corresponding to an annual per-patient cost of €8,275.[5]

Dr Sten Friberg, Nordic Medical Director, Eisai Europe Ltd commented; "Eisai is committed to bringing effective treatments to patients to help improve their quality of life, as displayed by our human health care mission. Studies have shown Zebinix to be effective in reducing seizure frequency and provide significant improvements to the patient's quality of life.[6,7,8,9,10,11] The launch will provide patients in Sweden with an effective option to manage their seizures."

Eslicarbazepine acetate was approved by the European Commission following data which showed that it reduces seizure frequency and has an overall positive efficacy and safety profile.[6-8] Eslicarbazepine acetate 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.

*Exclusively by BIAL

Notes to Editors

Zebinix^® is the EU trade name for eslicarbazepine acetate

Zebinix^® is under license from 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.[12]

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,[13] but may become more generalised;[13] the symptoms vary according to the affected areas.[14]

Treatment of partial-onset seizures, the most common type of epilepsy, presents a constant challenge - Up to 30% of patients with partial seizures do not achieve remission despite appropriate therapy with anti-epileptic drugs.[15] Hence, there is a need for new anti-epileptic agents that offer effective reduction in seizure frequency.

About Zebinix^®(eslicarbazepine acetate)

Eslicarbazepine acetate is indicated as adjunctive therapy in adults with partial-onset seizures with or without secondary generalisation.[1] Eslicarbazepine acetate is a once-daily, voltage-gated sodium channel blocker.[16] It selectively targets the inactivated state of the sodium ion channel, preventing its return to the active state, and thereby reduces repetitive neuronal firing.[16] Recent studies have also demonstrated that eslicarbazepine acetate effectively inhibits voltage-gated calcium channels, therefore enhancing its potential as an anti-epileptic agent.[17] The efficacy of eslicarbazepine acetate was demonstrated in an initial proof-of-concept phase II study[18] and three subsequent phase III randomised, placebo controlled studies in 1049 patients with refractory partial onset seizures.[6-8]

Clinical data

The EU approval was based on data from a phase II and three phase III clinical trials.[6-8,18] 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.[6-8]

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.[6-11]

Efficacy

Over the 12-week maintenance period, Zebinix^® 800mg and 1200mg once-daily significantly reduced seizure frequency, and was significantly more effective than placebo.[6-8,18]  Long-term safety and maintenance of therapeutic effect was demonstrated in one-year open-label extensions of these studies.[9-11]

Tolerability and drug interactions[6-8,18]

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 (Headquarters: London, President & CEO: Gary Hendler), a European subsidiary of Eisai Co., Ltd. (Headquarters: Tokyo, President & CEO: Haruo Naito), 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, Chairman: Luís Portela & CEO: António Portela, "BIAL"), which gave Eisai Europe Limited rights to sell BIAL's anti-epileptic drug Zebinix^®(eslicarbazepine acetate) in Europe.

About Eisai Europe 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 the European market.

In Europe, Eisai currently has three marketed treatments:

• Zonegran^® (zonisamide) as adjunctive therapy in adult patients with partial-onset seizures, with or without secondary generalisation
• Zebinix^® (eslicarbazepine acetate) as adjunctive therapy in adult patients with partial-onset seizures, with or without secondary generalisation (Zebinix is under licensed from BIAL)
• Inovelon^® (rufinamide) for the adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome in patients >4 years

About Eisai

Eisai is one of the world's leading R&D-based pharmaceutical companies and 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 recently expanded their UK Hatfield facility which now supports the company's growing European, Middle Eastern and African (EMEA) business.

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

• Neuroscience, including: Alzheimer's disease, multiple sclerosis, neuropathic pain, epilepsy, depression
• Oncology including: anticancer therapies; tumour regression, tumour suppression, antibodies, etc and supportive cancer therapies; pain relief, nausea
• Vascular/Immunological reaction including: acute coronary syndrome, atherothrombotic disease, rheumatoid arthritis, psoriasis, Crohn's 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, and Belgium.

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 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. Summary of Product Characteristics Zebinix® (eslicarbazepine acetate) (updated November 2011)

2. Titlic, M. Basic, S. Hajnek, S. Comorbidity psychiatric disorders in epilepsy: a review of literature. Bratisl Lek Listy (Bratislava Medical Journal) 2009; 110 (2): 105 - 109

3. Epilepsy must become a higher priority in Europe. The Lancet Neurology. 2010 Oct; 9(10): 941

4. Svenska Epilepsiförbundet. Worthwhile to know about epilepsy. http://epilepsi.se/Worthwhile-to-know-about-epilepsy.html (accessed May 2012)

5. Bolin K, Lundgren A, Berggren F, Källén K. Epilepsy in Sweden: health care costs and loss of productivity-a register-based approach. Eur J Health Econ. 2011 http://www.ncbi.nlm.nih.gov/pubmed/22042322 (Accessed May 2012)

6. 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.

7. 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.

8. Gil-Nagel A, Lopes-Lima J, Maia J 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: 281-287.

9. Halász P, Elger C, Guekht A, et al. Long-term efficacy and safety of eslicarbazepine acetate: Results of a 1-year open-label extension study in partial-onset seizures in adults with epilepsy.  Epilepsia, 51(10):1963-1969, 2010.

10. 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.

11. 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.

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

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

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

15. Rauchenzauner M, Luef G. Update on the treatment of partial onset epilepsy: a role of eslicarbazepine. Neurophsyiactric Disease and Treatment. 2010 Nov; 6(1): 723-730

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

17. Brady K et al. The effects of Eslicarbazepine, R-Licarbazepine, Oxcarbazepine and Carbamazepine on ion transmission through Cav3.2 channels.  Abstract presented at International Epilepsy Congress 2011 p858.

18. Elger et al. Eslicarbazepine Acetate: A Double-blind, Add-on Placebo-controlled Exploratory Trial in Adult Patients with Partial-onset seizures. Epilepsia, 48(3):497-504, 2007