Bial Announces Zebinix® (eslicarbazepine acetate) Meets Primary Endpoint in Phase 3 Monotherapy Study for Patients With Newly Diagnosed Partial-Onset Seizures

Porto, Portugal (ots/PRNewswire) -

PRESS RELEASE FOR EU MEDIA ONLY

Bial - Portela & Cª., S.A. (Bial) is pleased to announce positive
results for a pivotal phase 3 non-inferiority study comparing the
efficacy and safety of eslicarbazepine acetate (ESL) to controlled
release carbamazepine (CBZ-CR) as monotherapy in newly diagnosed
adult patients with partial-onset seizures (POS).

"The study met its primary endpoint, which was the proportion of
seizure-free patients for six consecutive months under monotherapy
treatment. This is an important addition to the well-known value of
ESL as adjunctive therapy. The complete study results will shortly be
disclosed at major neurology and epilepsy conferences and published
in specialized journals in the field," said Professor Patrício
Soares-da-Silva, Director of Research & Development Department at
Bial.

"The efficacy of ESL was clearly demonstrated in a high proportion
of patients that remained seizure-free for six consecutive months,
which was non-inferior to the seizure-free rate observed in patients
treated with CBZ-CR, positioning ESL as a first-line treatment for
newly diagnosed patients with focal epilepsies.", said Professor
Eugen Trinka, principal study coordinator and ?Chairman of the
Department of Neurology, Paracelsus Medical University, CDK,
Salzburg, Austria.

"This study reflects our commitment to the development of new
treatment options for people living with focal epilepsies", said
António Portela, CEO of Bial Group.

This pivotal phase 3 study was a randomised, double-blind,
parallel-group, active-controlled and non-inferiority study,
investigating the efficacy and safety of once-daily ESL (800 to 1600
mg/daily) as monotherapy treatment for newly diagnosed adults with
partial-onset seizures in comparison with twice-daily CBZ-CR (400 to
1200 mg/daily).

Based on these results, Bial intends to submit in the second
quarter of 2016 a variation file to the European Medicines Agency
(EMA), to expand the marketing authorization of eslicarbazepine
acetate (ESL) as monotherapy in adults with partial-onset seizures.

ESL is currently approved by the European Medicines Agency
(tradename Zebinix®). Eslicarbazepine acetate is indicated as
adjunctive therapy in adults with partial onset seizures, with or
without secondary generalisation (1). ESL is also approved by the US
Food and Drug Administration (tradename Aptiom®) for the treatment of
POS as monotherapy or adjunctive therapy (1, 2).

Notes to Editors

About epilepsy, partial-onset seizures and their treatment

Epilepsy is a chronic neurological disease characterized 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 generalized to involve the whole body. Patients
may also experience abnormal sensations, altered behaviour or altered
consciousness. Epilepsies are disorders with many possible causes.
Often the cause of epilepsy remains unknown even after intense
investigations. 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 (or focal) 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 sustained seizure control with current
anti-epileptic drugs (3).

About eslicarbazepine acetate (Zebinix® / Aptiom®)

Eslicarbazepine acetate is a once-daily anticonvulsant,
extensively and rapidly converted to eslicarbazepine after oral
administration (4). Eslicarbazepine reduces voltage-gated sodium
channels availability through enhancement of slow inactivation and
blocks T-type voltage-gated calcium channels (1, 5).

Eslicarbazepine acetate is currently marketed in Europe by
BIAL-Portela & Cª, S.A and by BIAL´s licensee, Eisai Europe Limited,
a European subsidiary of Eisai Co., Ltd. under the trade name
Zebinix®. In the United States and Canada eslicarbazepine acetate
(tradename Aptiom®) is marketed by Sunovion Pharmaceuticals Inc.,
under an exclusive license from BIAL. Eslicarbazepine acetate is
approved by the US Food and Drug Administration (tradename Aptiom®)
for the treatment of POS as monotherapy or adjunctive therapy (2).
The approval of Aptiom as monotherapy for partial-onset seizures was
supported by data from two pivotal Phase 3 clinical trials (Studies
093-045 and 093-046). Both trials met the pre-specified primary
endpoint agreed upon with the FDA.

Clinical data

The EU approved file for the use of eslicarbazepine acetate as
adjunctive treatment is based on efficacy and safety data from an
initial proof-of concept phase II study (6) and four subsequent phase
III randomized, placebo controlled studies in more than 1700 patients
with refractory partial-onset seizures (7-10). These patients had a
history of at least four partial-onset seizures per month despite
treatment with up to three concomitant anti-epileptic drugs (7-10).

Efficacy

Over the 12-week maintenance period, eslicarbazepine acetate 800mg
and 1200mg once-daily used adjunctively significantly reduced seizure
frequency, and was significantly more effective than placebo (7-10).
Long-term safety and maintenance of therapeutic effect was
demonstrated in one-year open-label extensions of these studies (11,
12).

Tolerability

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 (7-10).
After 6 weeks of treatment, there were no observed differences in the
incidence of side effects between patients treated with
eslicarbazepine acetate and the placebo group. Treatment-emergent
adverse events affecting >10% of patients in the pivotal studies were
dizziness and somnolence (1, 7-10).

Quality of life and depressive symptoms

The effect of eslicarbazepine acetate on quality of life was
assessed using the Quality of Life in 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 and improvements in individual elements of the QOLIE-31 scale
including seizure worry, emotional wellbeing, energy/fatigue,
medication effects and social function (11, 12). Improvement in
depressive symptoms was also measured using the Montgomery-Asberg
Depression Rating Scale (MADRS). During long-term, open-label
therapy, eslicarbazepine acetate demonstrated a statistically
significant improvement from baseline in the overall MADRS score and
individual items of the MADRS scale including pessimistic thoughts,
concentration difficulties, apparent sadness and inner tension (11,
12).

About BIAL Group

BIAL is a research based, privately owned, international
pharmaceutical group with products available in more than 50
countries.

Strongly committed to therapeutic innovation, BIAL´s research and
development (R&D) is focused on the central nervous system,
cardiovascular system and allergic immunotherapy, and currently has
several innovative programs under development, which it expects to
bring to the market within the next years. The R&D projects of the
company are also focused on the ongoing clinical development program
of eslicarbazepine acetate, which is already commercialised in the
United States and in several European markets. This program comprises
studies designed to evaluate new therapeutic indications, such as
adjuvant treatment in children and monotherapy.

Additionally Bial has completed the clinical development of
opicapone, a compound to treat patients living with Parkinson's
disease. This new drug is currently under evaluation by EMA.

For additional information on BIAL, please visit the company's web
site at: http://www.bial.com

References:

1. European Medicines Agency. Zebinix® (eslicarbazepine acetate): EU
summary of product characteristics. Available from:http://www.ema
.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information
/human/000988/WC500047225.pdf (accessed 2 December 2015)
2. Sunovion Pharmaceuticals Inc. Aptiom® (eslicarbazepine acetate)
tablets, for oral use: US prescribing information. Available
from:http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022
416s001lbl.pdf (accessed 2 December 2015).
3. Brodie MJ, Barry SJ, Bamagous GA et al. Patterns of treatment
response in newly diagnosed epilepsy. Neurology.
2012;15;78(20):1548-54.
4. Bialer M, Soares-da-Silva P. Pharmacokinetics and drug
interactions of eslicarbazepine acetate. Epilepsia
2012;53(6):935-46.
5. Soares-da-Silva P, Pires N, Bonifácio MJ, et al. Eslicarbazepine
acetate for the treatment of focal epilepsy: an update on its
proposed mechanisms of action. Pharmacol Res Perspect 2015; 3:
e00124.
6. Elger C, Bialer M, Cramer J et al. Eslicarbazepine acetate: a
double-blind, add-on placebo-controlled exploratory trial in
adult patients with partial-onset seizures. Epilepsia.
2007;48(3):497-504.
7. 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.
8. Ben-Menachem E, Gabbai A, Hufnagel A et al. Eslicarbazepine
acetate as adjunctive therapy in adult patients with partial
epilepsy. Epilepsy Research. 2010;89:278-285.
9. Lopes-Lima J, Gil-Nagel A, 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
Neurologica Scandinavica. 2009;120:281-287.
10. Sperling MR, Abou-Khalil B, Harvey J, et al. Eslicarbazepine
acetate as adjunctive therapy in patients with uncontrolled
partial-onset seizures: Results of a phase III, double-blind,
randomized, placebo-controlled trial. Epilepsia. 2015;56:244-253.
11. 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. 2010;51(10):1963-1969.
12. Hufnagel A, Ben-Menachem E, Gabbai AA et al. Long-term safety and
efficacy of eslicarbazepine acetate as adjunctive therapy in the
treatment of partial-onset seizures in adults with epilepsy:
results of a 1-year open-label extension study. Epilepsy
Research. 2013;103(2-3):262-9.

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

Contact:
Susana Vasconcelos Communication Manager susana.vasconcelos@bial.com
Rui Sousa International Medical Affairs Manager rui.sousa@bial.com
Bial - Portela & Cª
S.A. + 351 22 986 6100 À Av. da Siderurgia Nacional 4745-457 Coronado
(S. Romão e S. Mamede) PORTUGAL