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) in London.[1]
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 drugs.[2]
Eslicarbazepine acetate in Partial-Onset Seizures study
(EPOS)[3]
Launched in March 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 in Denmark,
France, Germany, Norway, Sweden and 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 both sides of the
brain).[1] 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 carbamazepine in adults with
partial-onset seizures.[4]
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 use in partial-onset seizures in Europe.[5]
The study aims to assess the efficacy and safety of eslicarbazepine
acetate as adjunctive therapy in 252 children and adolescents (2 -
18 years old).[5]
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 in Europe in 2009,
Zebinix is currently available in Albania*, 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®) and Wales.
*Exclusively by BIAL
Notes to Editors
Zebinix® is the EU trade name for
eslicarbazepine acetate
Zebinix® 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, the
symptoms vary according to the affected areas.[8]
Epilepsy is one of the world's most common neurological
disorders, affecting more than six million people across
Europe.[9] With
significant health care costs and economic impacts[10],
uncontrolled seizures also increase the risk of psychological
comorbidities, such as anxiety and depression.[11]
About Zebinix®(eslicarbazepine
acetate)
Eslicarbazepine acetate is a voltage-gated sodium channel
blocker.[12] It preferably targets the inactivated state
of the sodium ion channel, preventing its return to the active
state, and thereby reduces repetitive neuronal
firing.[12] Recent studies have
also demonstrated that eslicarbazepine acetate effectively inhibits
voltage-gated calcium channels, therefore enhancing its potential
as an anti-epileptic agent.[13] 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.[15],[16],[17]
Clinical data
The EU approval was based on data from a phase II and three
phase III clinical
trials.[11],[12],[13],[14]
Patients recruited in the phase III trials had a history of at
least four partial seizures per month despite treatment between one
to three concomitant anti-epileptic
drugs.[12],[13],[14]
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.[12],[13],[14],[18],[19],[20]
Efficacy
Over the 12-week maintenance period, Zebinix® 800mg
and 1200mg once-daily significantly reduced seizure frequency, and
was significantly more effective than
placebo.[11],[12],[13],[14]
Long-term safety and maintenance of therapeutic effect was
demonstrated in one-year open-label extensions of these
studies.[15],[16],[17]
Tolerability[11],[12],[13],[14]
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 in February 2009 that 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) 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 AEDs is a major strategic area for
Eisai in Europe, the Middle East, Africa and 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, Europe
and its domestic home market of Japan, Eisai employs more than 11,000 people
worldwide. 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, Slovakia,
the Netherlands, Belgium, Luxembourg, the Middle East and Russia.
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 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. Summary of Product Characteristics
Zebinix® (eslicarbazepine acetate)(updated November 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
(accessed March 2012)
7. Epilepsy Action. Describing Seizure
Types. http://www.epilepsy.org.uk/info/seizures/ataglance
(Accessed March 2012)
8. NHS Choices. Symptoms of Epilepsy.
http://www.nhs.uk/Conditions/Epilepsy/Pages/Symptoms.aspx
(Accessed March 2012)
9. Epilepsy must become a higher
priority in Europe. The Lancet
Neurology. 2010 Oct; 9(10): 941
10. Pugliatti M et al. Estimating the
cost of epilepsy in 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