Zebinix(R) Now Available in Greece

By Eisai Limited, PRNE
Sunday, April 17, 2011

Novel Once-Daily Anti-Epileptic Treatment

HATFIELD, England, April 19, 2011 - Zebinix(R) (eslicarbazepine acetate), an add-on (adjunctive) therapy for
adults with partial-onset seizures, with or without secondary generalisation
(where the seizure extensively affects consciousness of the patients by
propagation to both sides of the brain), has recently been launched in Greece
by Arriani Pharmaceuticals, Eisai's chosen partner in Greece.

In April 2009, the European Commission approved Zebinix(R) based on data
showing that it reduces seizure frequency and improves health-related quality
of life.[1],[2]

An estimated 100,000 people are affected by epilepsy in Greece.[3]
Epilepsy is one of the most common neurological diseases and successful
treatment of partial-onset seizures (the most common type of epilepsy)
remains a challenge. Up to 30% of patients with partial seizures do not
achieve remission despite appropriate therapy with anti-epileptic drugs.[4]

"There are many patients with epilepsy that do not see an improvement in
seizure control with existing anti-epileptic drugs. The launch of Zebinix(R)
in Greece permits a wider choice of anti-epileptic drugs to be better matched
to the individual patient. Zebinix(R) is shown to decrease seizure frequency
and improve health-related quality of life for patients with poor seizure
control. Eisai's human health care mission gives first thought to patients
and their families to improve their quality of life by bringing valuable
treatment that health care provides" commented Dr. Bettina Bauer, Head of EU
Epilepsy Business Unit, Eisai Europe Ltd.

Since its launch in mid 2009, Zebinix(R) had over 21,000
months of patient exposure.[5] Zebinix(R) is already available in Germany,
Austria, United Kingdom, Denmark, Norway, Iceland, Sweden, Portugal*,
Albania*, Cyprus*, Malta*, Spain (co promotion with BIAL, the developer of
Zebinix (R)), Republic of Ireland and Greece.

* Exclusively by BIAL

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 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.[6]

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,[7]
but may become more generalised;7 the symptoms vary according to the affected

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.[4]

Furthermore, central nervous system related adverse events,
such as lightheadedness (dizziness), somnolence (sleepiness), and cognitive
slowing (attention and memory deficits), are highly prevalent with existing
anti-epileptic agents.[9],[10],[11] 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(R) (eslicarbazepine acetate)

Zebinix(R) is indicated as adjunctive therapy in adults with
partial-onset seizures with or without secondary generalisation.1 Zebinix(R)
is a novel, once-daily, voltage-gated sodium channel blocker.[12],[13] It
preferably targets the inactivated state of the sodium ion channel,
preventing its return to the active state, and thereby reduces repetitive
neuronal firing.[13] The efficacy of Zebinix(R) 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.[12],[15],[16] Zebinix(R) 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

Clinical data

The EU approval was based on data from a phase II and three
phase III clinical trials.5,14,15,16 Patients recruited in the phase III
trials had a history of at least four partial seizures per month despite
treatment with up to three concomitant anti-epileptic drugs.[14],[15],[16]

During the trials, patients were randomised to various dosages
of Zebinix(R) 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.[14],[15],[16]


Over the 12-week maintenance period, Zebinix(R) 800mg and
1200mg once-daily significantly reduced seizure frequency, and was
significantly more effective than placebo.12,15,16,22 Long-term safety and
maintenance of therapeutic effect was demonstrated in one-year open-label
extensions of these studies.[22],[23],[24]

Tolerability and drug interactions[1],[12],[14],[15],[16],[19]

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. During the first
few weeks of treatment there were no observed differences in the incidence of
side effects between patients treated with Zebinix(R) and the placebo group.
The most common treatment-emergent adverse events in the pivotal studies were
dizziness, headache and somnolence.

Quality of life and depressive symptoms[17],[18],[19],[20],[21]

The effect of Zebinix(R) 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 (p<0.001 - p<0.01 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

Improvement in depressive symptoms was also measured using the
Montgomery Asberg Depression Rating Scale (MADRS). During long-term,
open-label therapy, Zebinix(R) demonstrated a statistically significant
improvement from baseline in the overall MADRS score (p<0.0001) and
individual domains of the MADRS scale including pessimistic thoughts,
concentration difficulties, apparent sadness and inner tension.

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 & C(a), S.A.
(Headquarters: Sao. Mamede do Coronado, Portugal, Chairman: Luis Portela &
CEO: Antonio Portela, "BIAL"), which gave Eisai Europe Limited rights to sell
BIAL's anti-epileptic drug Zebinix(R) (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 anti-epileptic drugs (AEDs) is a major strategic area for
Eisai in the European market.

In Europe, Eisai currently has three marketed treatments

- Zonegran(R) (zonisamide) as adjunctive therapy in adult
patients with partial-onset seizures, with or without secondary

- Zebinix(R) (eslicarbazepine acetate) as adjunctive therapy
in adult patients with partial-onset seizures, with or without secondary

- Inovelon(R) (rufinamide) for the treatment of seizures
associated with Lennox-Gastaut Syndrome

About Eisai

Eisai is one of the world's leading R&D-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 R&D 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 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. 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(R)).

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 www.bial.com


[1] Zebinix 800mg tablets - Summary of Product Characteristics (SPC):
Last updated 10 January 2011) Available from URL:
www.medicines.org.uk/emc/medicine/22376/SPC/ (Accessed 29 March 2011)

[2] Cramer JA, Elger C, Halasz P, et al, editors. An evaluation of
quality of life and depressive symptoms during long-term treatment with
eslicarbazepine acetate: BIA-2093-301 study [abstract 3.197]. American
Epilepsy Society Congress; 2008 5-9 December; Seattle, WA.

[3] Greek Association Against Epilepsy. What is epilepsy? Available from
URL: www.greece-epilepsy.com

(Accessed 28 February 2011)

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

[5] Eisai Europe Ltd. Data on file. Zebinix® PSUR of period 22-Apil-2010
to 21-October-2010

[6] Epilepsy Research UK. What is Epilepsy? Fact sheet. Avaiable from
URL: www.epilepsyresearch.org.uk/about_us/leaflets/lflt1.htm (accessed
March 16 2011)

[7] Epilepsy Action. Describing Seizure Types. Avaiable at URL
www.epilepsy.org.uk/info/seizures/ataglance (Accessed March 16 2011)

[8] NHS Choices. Symptoms of Epilepsy. Available at URL
www.nhs.uk/Conditions/Epilepsy/Pages/Symptoms.aspx (Accessed March 16

[9] Topamax Summary of Product Characteristics. Available at:
www.medicines.org.uk/emc/medicine/6768 (Accessed March 18 2011)

[10] Carbamazepine Summary of Product Characteristics. Available at:
200mg%2c+Tegretol+Tablets+100mg%2c+200mg%2c+400mg/ (Accessed March 18 2011)

[11] Oxcarbazepine Summary of Product Characteristics. Available at:
www.medicines.org.uk/emc/medicine/2673/SPC/#INDICATIONS (Accessed
March 18 2011)

[12] 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.

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

[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] 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.

[16] 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.

[17] 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.

[18] 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.

[19] 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.

[20] 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.

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

[22] 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.

[23] 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.

[24] 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.

For further information please contact: Benjamyn Tan / Helen Swift, Tonic Life Communications, +44(0)20-7798-9262, benjamyn.tan at toniclc.com / helen.swift at toniclc.com; Eisai Europe Ltd - Cressida Robson: +44(0)845-676-5318

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