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Data Demonstrates Long-Term Reduction In Seizure Frequency With Novel Once Daily Anti-Epileptic Zebinix(R)

June 29, 2009

S. MAMEDE DO CORONADO, Portugal, June 29 /PRNewswire/ — Data presented
today, in Budapest, demonstrated that add-on treatment with the novel,
once-daily anti-epileptic Zebinix(R)* (eslicarbazepine acetate; ESL) resulted
in a marked and sustained decrease in seizure frequency over the long-term(1).

Results from the one-year extension of a pivotal Eslicarbazepine Acetate
phase III study were presented at the International Congress for Epilepsy in
Budapest, Hungary. Patients not controlled with existing anti-epileptic drugs
who were given eslicarbazepine acetate as an add-on treatment experienced a
mean reduction in seizure frequency of more than 61% (95%CI: -68.2%,
-55.5%)1. Nearly 65% of patients were classified as responders, meaning that
they had achieved at least a 50% reduction in seizure frequency with
Zebinix(R) treatment(1).

“These data continue to demonstrate the efficacy and safety of Zebinix(R)
in the treatment of partial onset seizures”, said Joyce Cramer, research
scientist at Yale University School of Medicine, USA and President of The
Epilepsy Therapy Project. “Epilepsy is a devastating condition that can be
very difficult to manage and the availability of eslicarbazepine acetate adds
an important new choice of therapy for patients who are in vital need of
better seizure control.”

Epilepsy is one of the most common neurological diseases, affecting
approximately one in 100 people6. Treatment of partial-onset seizures, the
most common type of epilepsy, remains a constant challenge and up to 40% of
patients with partial seizures do not achieve seizure control with current
anti-epileptics(2).

Additional studies presented at the IEC further reinforce the efficacy
and safety of eslicarbazepine acetate in the treatment of partial-onset
seizures, with or without secondary generalisation(3,4).

Pooled data from more than 1,000 patients enrolled in the three pivotal
phase III studies demonstrated that add-on therapy with once-daily Zebinix(R)
(800mg and 1200mg) was effective in reducing partial-onset seizures in
patients not controlled with one of the most commonly used anti-epileptics,
carbamazepine (CBZ), (p<0.01 and p<0.0001 respectively)(3).

Across the clinical studies conducted, eslicarbazepine acetate has
demonstrated a favourable safety profile(5). This has been further reinforced
by a pooled analysis indicating that most adverse events begin within the
first weeks of treatment but after six weeks, no relevant difference was
found between eslicarbazepine acetate and placebo(4).

Zebinix(R), researched and developed by BIAL, received marketing
authorisation from the European Commission in April 2009, as adjunctive
therapy in adults with partial-onset seizures, with or without secondary
generalisation. Under the terms of a deal with BIAL, announced in February
this year, Eisai Europe Ltd received a sole license to market, promote and
distribute ESL within Europe**. Eisai and BIAL plan to launch Zebinix(R)
across Europe during 2009 and into 2010, providing a novel and effective
treatment to patients with partial-onset seizures who are not adequately
controlled with their existing medications. The rights to commercialise the
product in the U.S. and Canadian markets were licensed to Sepracor Inc., in
late 2007 (the proposed name for eslicarbazepine acetate in the U.S. and
Canada is STEDESA(TM)). In June 2009, Sepracor announced that the U.S. Food
and Drug Administration (FDA) accepted for filing its New Drug Application
(NDA) for STEDESA(TM) as adjunctive therapy in the treatment of partial-onset
seizures in adults with epilepsy, and the NDA is currently under formal
review.

Notes to Editors

* Zebinix(R) is the EU trade name for eslicarbazepine acetate.

** European Territories

Austria, Belgium, Bulgaria, Czech Republic, Belarus, Bosnia, Croatia,
Denmark, Estonia, Finland, France, Germany, 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 United Kingdom.

About epilepsy, partial-onset seizures and their treatment

Epilepsy is one of the most common neurological diseases, affecting
approximately 1 in 100 people(6).

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 neurone 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(2).

Furthermore, adverse events, such as lightheadedness (dizziness),
somnolence (sleepiness), and cognitive slowing, are highly prevalent with
existing anti-epileptic agents and may affect as many as 97% of patients(7).
Hence, there is a need for new anti-epileptic agents that offer effective
reduction in seizure frequency combined with a favourable safety profile.

About Eslicarbazepine Acetate

Eslicarbazepine acetate (ESL) is a novel once-daily voltage-gated sodium
channel blocker designed to selectively inhibit the rapid firing of nerve
cells that causes seizures. It specifically targets the inactivated state of
the ion channel, preventing its return to the active state, and thereby
reduces repetitive neuronal firing. The efficacy of ESL has been demonstrated
in three randomised, placebo controlled studies in 1049 patients with
refractory partial onset seizures. ESL 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 3 studies. ESL is given
orally once-daily. ESL can be used as an add-on to carbamazepine (one of the
most commonly utilized therapies for partial onset seizures) or with other
anti-epileptics.

Clinical data

The EU approval was based on data from phase II and three phase III,
double-blind, randomised, placebo-controlled, multi-centre trials involving
1,192 patients from 23 countries. Patients 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 ESL 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.

Efficacy

Over the 12 week maintenance period, ESL 800mg and 1200mg once-daily
reduced seizure frequency by over one third, and was significantly more
effective than placebo. This significant decrease in seizure frequency was
sustained over the one-year open label treatment period and was consistent
regardless of baseline therapy.

Tolerability

The safety profile of ESL was favourable. The majority of treatment
related adverse events were mild or moderate in intensity. After 6 weeks of
treatment, there were no observed differences in the incidence of side
effects between patients treated with ESL and the placebo group.

Quality of life and depressive symptoms

The effect of ESL 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(8).

Improvement in depressive symptoms was also measured using the Montgomery
Asberg Depression Rating Scale (MADRS). During long-term, open-label therapy,
ESL 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(8).

These data were presented at the 28th International Epilepsy Congress
held in Budapest, 28 June 20092 July 2009, the 8th European Congress on
Epileptology held in Berlin last September 2008 and at the Annual Meeting of
the American Epilepsy Society (AES) in December 2008, Seattle, WA, USA.

About BIAL

Founded in 1924, BIAL is an international pharmaceutical group with
products available in over 30 countries throughout four continents. BIAL is
the largest Portuguese pharmaceutical company and is based in S. Mamede do
Coronado, Portugal.

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
approximately 20% of its turnover in research and development every year. Key
research areas for BIAL are the central nervous system, the cardiovascular
system and allergology. 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. Elger C, Halász P, Moreira J et al. Long-term add-on treatment of
partial epilepsy with eslicarbazepine acetate. Abstract presented at the 28th
International Epilepsy Congress, Budapest, Hungary, 28 June 20092 July
2009
.

2. Brodie MJ. Management strategies for refractory localization-related
seizures. Epilepsia 2001; 42(Suppl 3):27-30.

3. Halász P, Elger C, Ben-Menachem E et al. Efficacy and safety of
eslicarbazepine acetate as add-on treatment to carbamazepine in patients with
partial-onset seizures. Abstract presented at the 28th International Epilepsy
Congress, Budapest, Hungary, 28 June 20092 July 2009.

4. Gama H, Elger C, Halász P et al. Time of occurence of adverse events
in relation to start of treatment with eslicarbazepine acetate as add-on
treatment in patients with partial-onset seizures. Abstract presented at the
28th International Epilepsy Congress, Budapest, Hungary, 28 June 20092
July 2009
.

5. 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. Poster presented
at the American Epilepsy Society (AES) Congress, 5-9 December 2008, Seattle,
WA
, USA (Epilepsia, 49(Suppl. 7), 1-498, 2008).

6. WHO Atlas: Epilepsy Care in the World. WHO 2005

7. Mei PA, Montenegro MA, Guerreiro MM, Guerreiro CA. Pharmacovigilance
in epileptic patients using antiepileptic drugs. Arq Neuropsiquiatr 2006
Jun;64(2A): 198-201. Epub 2006 Jun 9

8. Cramer J, Elger C, Halász P et al. An Evaluation of Quality of Life
and Depressive Symptoms During Long-Term Treatment with Eslicarbazepine
Acetate: BIA-2093-301 Study.QOL 301. Poster presented at the American
Epilepsy Society (AES) Congress, 5-9 December 2009, Seattle, WA, USA
(Epilepsia, 49(Suppl. 7), 1-498, 2008).

    For further information please contact
    Media contacts
    For more information please contact:
    BIAL (head office)
    Francisco Osório
    Tel.: +351-22-986-6100
    Mobile: +351-96-346-9968
    francisco.osorio@bial.com

    Pat Pearson
    Red Health
    Tel.: +44-207-025-6572
    Mobile: +44-7734406688
    par.pearson@redconsultancy.com

SOURCE BIAL


Source: newswire



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