Final EPOS Study Results Published in Acta Neurologica Scandinavica Show Anti-epilepsy Treatment Zebinix® (Eslicarbazepine Acetate) Administered as Only Add-on to a Current Monotherapy Leads to High Retention and Seizure Freedom Rates and is Well-tolerated in Everyday Clinical Practice

HATFIELD, England, February 29, 2016 /PRNewswire/ --

PRESS RELEASE FOR EU MEDIA ONLY: NOT FOR SWISS/AUSTRIAN/U.S. JOURNALISTS  

Final results of the European non-interventional study EPOS (Eslicarbazepine acetate in Partial-Onset Seizures) show that once-daily eslicarbazepine acetate can provide a significant decrease in seizure frequency and seizure freedom in many patients, and is well tolerated in clinical settings. The responder rate (proportion of patients with seizure reduction of 50% and above vs. baseline) at six months was 81.8%, with 39.2% of patients reporting seizure freedom. The retention rate after 6 months was high with 82.2%.Over the 6 month study period, the score of the quality of life inventory QOLIE-10 improved from 2.9 at baseline to 2.1 at study end, on group level. These data were published today in Acta Neurologica Scandinavica, one of the leading epilepsy journals.^[1]

EPOS is a non-interventional, multicentre, prospective study with adult patients suffering from partial-onset seizures insufficiently controlled by antiepileptic monotherapy (n=247). Retention, tolerability and safety, efficacy, as well as effects on health-related quality of life of eslicarbazepine acetate as only add-on therapy were assessed. The study was conducted in eight European countries (UK, Ireland, Denmark, Sweden, Norway, France, Czech Republic and Germany).^[1]

"The results show that with this add-on treatment, we can offer patients with focal epilepsy inadequately controlled by monotherapy a chance to improve their condition. The high retention rate reflects treatment satisfaction, and points to an efficacious and well tolerable therapy, which is easy to initiate. Approximately one third of people with epilepsy do not achieve seizure freedom with monotherapies, so there is a continued need for additional efficacious treatment options," comments Martin Holtkamp, Principal Investigator, University Hospital Charité, Germany.

Eslicarbazepine acetate, indicated in Europe as adjunctive therapy in adults with partial-onset seizures, with or without secondary generalization^[2] is a once-daily drug and exerts its effect by a differential and selective action of its primary metabolite, eslicarbazepine, on sodium channels in their slow inactivated state. Eslicarbazepine acetate was approved by the European Commission in 2009 based on data submitted which showed that a significant therapeutic response could be reached by up to to 44% of difficult-to-treat patients with partial epilepsy.^[3] In long-term studies in patients with refractory epilepsy, it was shown that seizure freedom could be achieved by up to 12,5% of patients.^[4] Furthermore, experimental evidence documents an effect of eslicarbazepine in human brain tissue refractory to carbamazepine.^[5]  

Epilepsy is one of the most common neurological conditions, affecting approximately 6 million people in Europe.^[6] Despite many anti-epileptic drugs (AEDs) available, the successful treatment of partial onset seizures remains a significant challenge in some patients. Currently, between 20-40% of patients with newly diagnosed epilepsy will become refractory to treatment.^[7]

"People with epilepsy can face a struggle to control their seizures and maintain a good quality of life. We are extremely pleased that once-daily eslicarbazepine acetate has performed well in a real life clinical setting, is effective, well tolerated and helps patients to manage their seizures. Eisai is committed to provide effective treatments to patients, as underscored by our human health care mission," comments Neil West, Vice President, Global Neurology Business Unit, Eisai EMEA.

The continued development of eslicarbazepine acetate underscores Eisai's human health care (hhc) mission, the company's commitment to innovative solutions in disease prevention, cure and care for the health and wellbeing of people worldwide.

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^[®]

Notes to Editors   

About Zebinix^® (eslicarbazepine acetate)

Eslicarbazepine acetate is indicated as adjunctive therapy in adults with partial onset seizures, with or without secondary generalisation.^[6]The clinical trial programme is also underway for eslicarbazepine acetate as a paediatric and monotherapy treatment.

Eslicarbazepine acetate is a voltage-gated sodium channel blocker.^[8] It selectively targets the slow inactivated state of the sodium ion channel^[9],[10] (which have been implicated in the pathogenesis of epilepsy),^[11] preventing its return to the active state, and thereby reduces repetitive neuronal firing.^[9] Further, eslicarbazepine acetate does not inhibit potassium efflux,^[12] which may reduce the potential for repetitive neuronal firings.^[9] The efficacy of eslicarbazepine acetate was demonstrated in an initial proof-of-concept phase II study^[14] and three subsequent phase III randomised, placebo controlled studies in 1049 patients with refractory partial onset seizures.^[13],[2]

• Zebinix^® is the EU trade name for eslicarbazepine acetate
• Zebinix^® is under license from BIAL
• APTIOM^® is the U.S. and Canada trade name for eslicarbazepine acetate

For more information please visit: http://www.eisai.co.uk

About Epilepsy   

Epilepsy is one of the most common neurological conditions in the world, affecting approximately 6 million people in Europe, and an estimated 50 million people worldwide.^[14] Epilepsy is a chronic disorder of the brain that affects people of all ages. It is characterised by abnormal discharges of neuronal activity which causes seizures. Seizures can vary in severity, from brief lapses of attention or jerking of muscles, to severe and prolonged convulsions. Depending on the seizure type, seizures may be limited to one part of the body, or may involve the whole body. Seizures can also vary in frequency from less than one per year, to several per day. Epilepsy has many possible causes but often the cause is unknown.

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, Russia and Oceania (EMEA).

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

• Zebinix^® (eslicarbazepine acetate) as adjunctive therapy in adults with partial onset seizures, with or without secondary generalisation (Zebinix is under license from BIAL). Eisai received a sole license to market, promote and distribute Zebinix^® in the following European Countries: Austria, Belgium, Bulgaria, Czech Republic, Belarus, Bosnia, Croatia, Denmark, Estonia, Finland, France, Germany (co-promotion with Bial since May 2015), Greece, Hungary, Iceland, Ireland, Italy, Latvia, Liechtenstein, Lithuania, Luxembourg, Monaco, Netherlands, Norway, Poland, Romania, Russia, Serbia, Slovakia, Slovenia, Spain (co-promotion with Bial from launch) Sweden, Switzerland, Turkey, Ukraine and the United Kingdom (co-promotion with Bial since July 2015)
• Fycompa^® (perampanel) for the adjunctive treatment for partial onset seizures, with or without secondarily generalised seizures, in patients with epilepsy aged 12 years and older. Fycompa is also indicated for the treatment of primary generalised tonic-clonic (PGTC) seizures in adults and adolescents (≥12 years) with idiopathic generalised epilepsy (IGE)
• Zonegran^® (zonisamide) as monotherapy in the treatment of partial seizures, with or without secondary generalisation, in adults with newly diagnosed epilepsy and as adjunctive therapy in the treatment of partial seizures, with or without secondary generalisation, in adults, adolescents, and children aged 6 years and above (Zonegran is under license from the originator Dainippon Sumitomo Pharma)
• Inovelon^® (rufinamide) for the adjunctive therapy in the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients four years of age and older (Rufinamide was originally developed by Novartis)

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.

About BIAL   

Founded in 1924, BIAL's mission is to discover, develop and provide therapeutic solutions within the area of health. In recent decades, BIAL has focused on quality, innovation and internationalization. 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 several French- or Portuguese-speaking African countries.

BIAL is strongly committed to therapeutic innovation, investing more than 20% of its turnover in research and development (R&D) every year, placing it among the most innovative European companies. Key research areas for BIAL are the central nervous system, the cardiovascular system and allergen 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.

With a team of 900 employees, BIAL has reinforced its international presence, an aspect that the company will strengthen over the next decade.

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

References   

1. Holtkamp et al. Eslicarbazepine acetate as add-on treatment to antiepileptic monotherapy in adults with partial-onset seizures: real-world data on retention, dosing, patient reported seizure outcome and safety from an

   interim analysis of the open-label non-interventional study EPOS. Acta Neurologica Scandinavica 2016. Available at http://onlinelibrary.wiley.com/doi/10.1111/ane.12574/full (accessed February 2016) 

2. Eisai Ltd 2015. Zebinix® (eslicarbazepine acetate) summary of product characteristics (last updated May 2015): http://www.medicines.org.uk/emc/medicine/22376/SPC/Zebinix+800mg+tablets/

3. Gil-Nagel A et al. Efficacy and safety of eslicarbazepine acetate as add-on treatment in patients with focal-onset seizures: integrated analysis of pooled data from double-blind phase III clinical studies.

   Epilepsia 2013;54(1):98-107 

4. 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 

5. Doeser et al. Targeting pharmacoresistant epilepsy and epileptogenesis with a dual-purpose antiepileptic drug. Brain 2014;1:1 

6. ILAE/IBE/WHO, Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe 2010. Available at; http://www.ilae.org/Visitors/Documents/ILAEAnnual-Report2010Final_000.pdf (Accessed January 2015)  

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

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

9. Elger C et al. Pharmacokinetics and tolerability of eslicarbazepine acetate and oxcarbazepine at steady state in healthy volunteers. Epilepsia 2013; 54(8):1453-1461 

10. 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 Feb; 89:122-135.

    Doi 10.1016/j.neuropharm.2014.09.008. 

11. Vilin YY and Ruben PC. Slow Inactivation in Voltage-Gated Sodium Channels. Cell Biochem Biophys 2001; 35(2):171-190 

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

13. Ben-Menachem E et al. Eslicarbazepine acetate as adjunctive therapy in adult patients with partial epilepsy; Epilepsy Research 2010; 89:278-285 

14. Pugliatti M, et al. Estimating the cost of epilepsy in Europe: A review with economic modeling. Epilepsia 2007; 48(12) 2224-2233