Zebinix(R) Now Available in Greece

Hatfield, England (ots/PRNewswire) - 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 areas.[8]

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 studies.[17],[18],[19],[20],[21]

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]

Efficacy

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 function.

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 , 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: 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
including:

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

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

- 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
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. 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
http://www.bial.com

References

[1] Zebinix 800mg tablets - Summary of Product Characteristics
(SPC): Last updated 10 January 2011) Available from URL:
http://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: http://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:
http://www.epilepsyresearch.org.uk/about_us/leaflets/lflt1.htm
(accessed March 16 2011)

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

[8] NHS Choices. Symptoms of Epilepsy. Available at URL
http://www.nhs.uk/Conditions/Epilepsy/Pages/Symptoms.aspx (Accessed
March 16 2011)

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

[10] Carbamazepine Summary of Product Characteristics. Available
at: http://www.medicines.org.uk/EMC/medicine/1328/SPC/Tegretol+Chewta
bs+100mg%2c+ 200mg%2c+Tegretol+Tablets+100mg%2c+200mg%2c+400mg/
(Accessed March 18 2011)

[11] Oxcarbazepine Summary of Product Characteristics. Available
at: http://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. 2008;49(7):455-6.

[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, CzÅ?onkowska 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.

ots Originaltext: Eisai Limited
Im Internet recherchierbar: http://www.presseportal.de

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