Zebinix, Novel Once-Daily Anti-Epileptic Treatment, Launches in Spain

By Eisai Europe Limited, PRNE
Tuesday, February 8, 2011

HATFIELD, England, February 10, 2011 - Zebinix(R) (eslicarbazepine acetate), an add-on (adjunctive) therapy for
adults with partial-onset seizures, with or without secondary generalisation
(where the seizure spreads to both sides of the brain), has been launched
today in Spain by Eisai and BIAL in a co-promotion.

In 2009, the European Commission approved Zebinix based on data showing
that it reduces seizure frequency and improves health-related quality of

Epilepsy is one of the most common neurological diseases, affecting up to
400,000 people in Spain[2] - and the successful treatment of partial-onset
seizures (the most common type of epilepsy) remains a challenge. Up to 40% of
patients with partial seizures do not achieve seizure control with current

"There are many patients with epilepsy whose condition is difficult to
treat with existing anti-epileptic drugs. Zebinix, developed by BIAL, is the
outcome of its longstanding scientific commitment to CNS research and
development, and its launch in Spain now offers a new therapeutic option
which is shown to decrease seizure frequency and improve quality of life in
those patients with poor seizure control," commented Mark Duffy, Business
Development Director, BIAL

"Eisai's mission to regard patients and their families as the most
important participants in the healthcare process is demonstrated by our
continued commitment to epilepsy in Europe. By increasing our European
footprint, we are able to bring valuable treatment options to more patients
with epilepsy. The launch of Zebinix in Spain is a clear example of our
dedication to this therapeutic area," commented Dr. Bettina Bauer, Head of EU
Epilepsy Business Unit, Eisai Europe Ltd.

In its first year Zebinix has had over 9,000 months of patient
exposure.[4] Zebinix is already available in Germany, Austria, United
, Denmark, Norway, Iceland, Sweden, Portugal* Albania*, Cyprus*,
Malta* and Spain (co promotion with BIAL from launch).

*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. Clinically, these
manifest as convulsions or jerking of muscles. 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 abnormal brain development, 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 focused in specific areas of the brain, but
may become more generalised; the symptoms vary according to the affected
areas. Nerve impulses are triggered via voltage-gated sodium channels in the
nerve cell membrane.

Treatment of partial-onset seizures, the most common type of
epilepsy, presents a constant challenge - up to 40% of patients with
partial-onset seizures do not achieve seizure control with current
anti-epileptic drugs.3

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. 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 (eslicarbazepine acetate)

Zebinix is indicated as adjunctive therapy in adults with
partial-onset seizures with or without secondary generalisation.1 Zebinix is
a novel, once-daily, voltage-gated sodium channel blocker.[5],[6] It
preferably targets the inactivated state of the ion channel, preventing its
return to the active state, and thereby reduces repetitive neuronal
firing.5,6 The efficacy of Zebinix has been demonstrated an initial
proof-of-concept phase II study18 and three subsequent phase III randomised,
placebo controlled studies in 1049 patients with refractory partial onset
seizures.[5],[7],[8] Zebinix 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.[9],[10],[11],[12],
[13] Zebinix is given orally once-daily.

Clinical data

The EU approval was based on data from a phase II and three
phase III clinical trials. Patients in phase III had a history of at least
four partial seizures per month despite treatment with up to three
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 period.


Over the 12-week maintenance period, Zebinix 800mg and 1200mg
once-daily significantly reduced seizure frequency, and was significantly
more effective than placebo.[5,7,8,14] Long-term safety and maintenance of
therapeutic effect was demonstrated in one-year open-label extensions of
these studies.[15],[16],[17]


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. After 6 weeks of
treatment, there were no observed differences in the incidence of side
effects between patients treated with Zebinix and the placebo group.
Treatment-emergent adverse events affecting >10% of patients in the pivotal
studies were dizziness, headache and somnolence.

Quality of life and depressive symptoms[9],[10],[11],[12],[13]

The effect of Zebinix 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 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: 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(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 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).

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] European Medicines Agency. Zebinix (eslicarbazepine acetate): summary
of product characteristics. Available from URL:
ublic/human/000988/WC500047226.pdf (Accessed 2 November 2010)

[2] Asociacion de Afectados por la Enfermedad de Epilepsia Mioclonica
Progresiva de Lafora. Available from URL www.arrakis.es/~lafora/
(Accessed 1 February 2011)

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

[4] Eisai Europe Ltd. Data on file.

[5] 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.

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

[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] 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.

[9] 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.

[10] 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.

[11] 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.

[12] 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.

[13] 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.

[14] Elger C, French J, Halasz P. et al. Evaluation of Eslicarbazepine
Acetate as Add-On Treatment in Patients with Partial-Onset Seizures: Pooled
Analysis of Three Double-Blind Phase III Clinical Studies. (Abstract No.
3.199). Epilepsia. 2008;49(Suppl. 7):428-9.

[15] 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.

[16] 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.

[17] 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.

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

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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