New Studies on Zebinix® Presented at Leading European Epilepsy Congress

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• Publié par: eisai-europe-limited
• Nombre de lectures: 51
• Langue: English

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New Studies on Zebinix® Presented at Leading European Epilepsy Congress

PR Newswire HATFIELD, England, October 3, 2012

HATFIELD,England,October 3, 2012/PRNewswire/ -- Bial and Eisai today present information on new studies designed to increase ® the understanding of the use of Zebinix (eslicarbazepine acetate), a once- daily adjunctive therapy for adults with partial-onset seizures, with or without secondary generalisation, at the 10th European Congress on Epileptology (ECE) [1] inLondon. These new data will be important as the successful treatment of partial-onset seizures remains a challenge, and up to a third of people with epilepsy do not achieve freedom from seizures despite appropriate therapy with anti-epileptic [2] drugs. [3] Eslicarbazepine acetate in Partial-Onset Seizures study (EPOS) Launched inMarch 2012, the Eslicarbazepine acetate in Partial-Onset Seizures (EPOS) study design presented here aims to provide a better understanding of the use of eslicarbazepine acetate in a clinical practice setting. EPOS is a prospective, multicentre, open-label, non-interventional study of adults with partial-onset seizures insufficiently controlled by monotherapy anti-epileptic treatment. The goal is to recruit approximately 800 patients from over 200 centres inDenmark,France,Germany,Norway,Swedenand the UK. The study primary endpoint will be 6-month retention rate and other assessments will include seizure frequency, adverse events and quality of life. "The significant number of people with epilepsy who fail to achieve seizure control necessitates the need for on-going investigations in real life settings," commented Martin Holtkamp, EPOS Principal Investigator from the University Hospital Charité,Germany. "Our non-interventional study will increase our knowledge of eslicarbazepine acetate's efficacy and tolerability in routine practice when used to treat adults who are less refractory than those included in standard Phase III adjunctive therapy clinical trials. This will be very valuable information." Eslicarbazepine acetate is currently licenced as an adjunctive treatment for adults with partial-onset seizures, with or without secondary generalisations (where the seizure extensively affects a patient's consciousness by spreading to [1] both sides of the brain). It is not yet known whether eslicarbazepine acetate will demonstrate efficacy and tolerability if used as a monotherapy and in newly diagnosed patients. To address this question, also presented today is the design of a Phase III, double-dummy, active controlled, multinational non-inferiority monotherapy trial of eslicarbazepine acetate versus controlled-release [4] carbamazepine in adults with partial-onset seizures. This study will enrol newly diagnosed epilepsy patients ≥18 years of age with documented partial-onset seizures and randomise in a 1:1 ratio. Paediatric patients sometimes require specific dosing regimens, and additional safety and tolerability evidence beyond that available for adult populations is

required. Eslicarbazepine acetate, which does not have a paediatric licence, is currently under investigation in a paediatric patient population for adjunctive [5] use in partial-onset seizures inEurope. The study aims to assess the efficacy and safety of eslicarbazepine acetate as adjunctive therapy in 252 children and [5] adolescents (2 - 18 years old). There are a further 16 posters presented within this congress, many of which examine the pharmacokinetic and pharmacodynamic information pertaining to eslicarbazepine acetate. "It is great to see so many studies presented here at the ECE. The abstracts which focus on the pharmacokinetic and pharmacodynamic information will also help doctors build up a much clearer picture of eslicarbazepine acetate," said Professor Eugen Trinka from the Department of Neurology, Paracelsus Medical University,Salzburg, Austria. Approved inEuropein 2009, Zebinix is currently available inAlbania*,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 ) andWales. *Exclusively by BIAL

Notes to Editors

® Zebinixis the EU trade name for eslicarbazepine acetate ® Zebinixis 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 [6] damage to tumours, 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 [7] focused in specific areas of the brain, but may become more generalised, [8] the symptoms vary according to the affected areas. Epilepsy is one of the world's most common neurological disorders, affecting [9] more than six million people acrossEuropesignificant health care costs. With [10] and economic impacts , uncontrolled seizures also increase the risk of [11] psychological comorbidities, such as anxiety and depression. ® About Zebinix (eslicarbazepine acetate) [12] Eslicarbazepine acetate is a voltage-gated sodium channel blocker. It preferably targets the inactivated state of the sodium ion channel, preventing [12] its return to the active state, and thereby reduces repetitive neuronal firing.

Recent studies have also demonstrated that eslicarbazepine acetate effectively inhibits voltage-gated calcium channels, therefore enhancing its potential as an [13] anti-epileptic agent. The efficacy of eslicarbazepine acetate was [14] demonstrated in an initial proof-of-concept phase II study and three subsequent phase III randomised, placebo controlled studies in 1049 patients [15],[16],[17] with refractory partial onset seizures.

Clinical data

The EU approval was based on data from a phase II and three phase III clinical [11],[12],[13],[14] trials. Patients recruited in the phase III trials had a history of at least four partial seizures per month despite treatment between one to three [12],[13],[14] 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 [12],[13],[14],[18],[19],[20] period.

Efficacy

® Over the 12-week maintenance period, Zebinix 800mg and 1200mg once- daily significantly reduced seizure frequency, and was significantly more [11],[12],[13],[14] effective than placebo. Long-term safety and maintenance of therapeutic effect was demonstrated in one-year open-label extensions of [15],[16],[17] these studies. [11],[12],[13],[14] Tolerability 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 inFebruary 2009that 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) inEurope.

About Eisai Europe in Epilepsy:

Eisai is committed to developing and delivering highly beneficial new treatments to hel im rove the lives of eo le with e ile s . The develo ment

of AEDs is a major strategic area for Eisai inEurope, theMiddle East,Africaand 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,Europeand its domestic home market of Japan, Eisai employs more than 11,000 people worldwide. InEurope, 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, theMiddle EastandRussia. 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 inLatin Americaand in around 20 French or Portuguese speaking African countries. BIAL is stron l committed to thera eutic innovation investin 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 throughoutEurope. Further information about BIAL can be found at http://www.bial.com

References 1. Summary of Product Characteristics Zebinix® (eslicarbazepine acetate)(updatedNovember 2011) 2. Kwan P, Brodie MJ. Early identification of refractory epilepsy. New England Journal of Medicine 2000; 342:314-9 3. Holtkamp et al. Design of the EPOS Study. An Open Label Multicentre, Non-Interventional Study to Evaluate Eslicarbazepine Acetate as Adjunctive Treatment to One Baseline Antiepileptic Drud in Adults with Partial Onset seizures. ECE 2012 abstract p665

4. J. Moreira et al. Design of a Phase III, double-dummy, active-controlled, multi-national non-inferiority monotherapy trial of eslicarbazepine acetate versus controlled-release carbamazepine in adults with partial- onset seizures. Abstract ECE 2012 (p415). 5. F. Mota et al. A clinical study method used to evaluate the efficacy and safety of novel antiepileptic drug eslicarbazepine acetate in epileptic children with partial-onset seizures. Abstract ECE 2012 (p175). 6. Epilepsy Research UK. What is Epilepsy? Fact sheet.: http://www.epilepsyresearch.org.uk/about_us/leaflets/lflt1.htm (accessedMarch 2012) 7. Epilepsy Action. Describing Seizure Types.  (Accessed http://www.epilepsy.org.uk/info/seizures/ataglance March 2012) 8. NHS Choices. Symptoms of Epilepsy. http://www.nhs.uk/Conditions/Epilepsy/Pages/Symptoms.aspx (AccessedMarch 2012) 9. Epilepsy must become a higher priority inEurope. The Lancet Neurology. 2010 Oct; 9(10): 941

Europe: A review with economic modelling. Epilepsia 2007: 48(12) 2224 - 2233. 11. 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 12. Almeida L, Soares-da-Silva P. Eslicarbazepine acetate (BIA 2-093). Neurotherapeutics. 2007 Jan;4(1):88-96

13. 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. 14. 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 15. 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 16. 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. 17. 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

18. 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

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

20. 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.

Date of preparation:September 2012 Job code: Zebinix-UK2255