Data Presented at 12th European Congress on Epileptology (ECE) Offers New Insights into Seizure Control and Safety Profile of Zebinix® (eslicarbazepine acetate) in the Treatment of Newly Diagnosed Par

Porto, Portugal and Hatfield, England (ots/PRNewswire) -

FOR EMEA MEDIA ONLY - NOT FOR SWISS/AUSTRIAN/CZECH REPUBLIC
JOURNALISTS

Methodology also announced for large pan-European pooled analyses
of Zebinix® (eslicarbazepine acetate) real-world data to assess use
for partial epilepsy in clinical practice

Data from an investigational Phase III study for adjunctive
Zebinix® (eslicarbazepine acetate) in a monotherapy setting showed
that eslicarbazepine acetate is non-inferior to controlled release
(CR) carbamazepine in patients with newly diagnosed partial onset
seizures.[1] Eslicarbazepine acetate is currently indicated in Europe
as adjunctive therapy in adults with partial onset seizures, with or
without secondary generalisation.[2]

The non-inferiority study included 785 eligible patients (>=18
years) with newly diagnosed partial-onset seizures, who were
randomised to receive eslicarbazepine acetate or carbamazepine CR in
a three-step dose-level design. Dose-levels were maintained through a
26-week evaluation period and subjects who remained seizure-free at
any dose level continued through subsequent phases of the study. The
primary endpoint for the study was the proportion of patients with
26-week seizure freedom (non-inferiority difference margin of -12%)
in the per-protocol (PP) population.[1]

The study met the primary endpoint showing that in a monotherapy
setting, once-daily eslicarbazepine acetate is non-inferior to
twice-daily carbamazepine CR. Seizure freedom rates for the entire
26-week evaluation period with eslicarbazepine acetate were 71.1%
(n=388) and 75.6% (n=397) with carbamazepine CR (average risk
difference -4.28%, 95% CI -10.3, 1.74%).[1]

Results of a safety analysis from the same study were also
presented. Of 813 patients included in the analysis, the number of
patients experiencing at least one treatment emergent adverse event
was similar for eslicarbazepine acetate and carbamazepine CR (75.3%
vs 77.7% respectively) and the majority of events were mild. The most
frequently reported possibly-related treatment emergent adverse
events were headache (6.5% vs 5.6%), dizziness (7.2% vs 6.8%), nausea
(4.5% vs 6.8%), fatigue (4.7% vs 4.4%), somnolence (5.2% vs 7.0%) and
increased gamma-glutamyltransferase (2.7% vs 12.4%). Fewer subjects
discontinued treatment due to a treatment emergent adverse event in
the eslicarbazepine acetate group (13.5% vs 18.0%).[3]

"These data demonstrate that eslicarbazepine acetate has a similar
efficacy and safety profile to controlled-release carbamazepine. The
differing characteristics of epilepsy treatments matter, as striking
a good balance between achieving improvement in seizure control, with
manageable side effects, can mean the difference between a patient
continuing with treatment or not," comments Eugen Trinka, Professor
and Chair of Department of Neurology, Christian Doppler Klinik,
Paracelsus Medical University, Salzburg, Austria.

BIAL and Eisai also announced details of a new pan-European,
pooled analyses of real-world safety and efficacy data for patients
treated with adjunctive eslicarbazepine acetate, to complement
evidence from clinical trials.[4] The methodology of this analysis is
presented for the first time at ECE.

The data, compiled from pooled analyses of 'real-world' databases
across Europe, including Spain, Portugal, France, Germany, UK,
Ireland, Czech Republic, and the Nordics, will provide further
information regarding seizure freedom, responder rate (>=50% seizure
frequency reduction), tolerability, quality of life and global
improvement, dosing, and treatment duration in patients treated with
adjunctive eslicarbazepine acetate for partial-onset seizures.
Subgroup analyses, including the assessment of elderly patients,
comorbidities (such as depression and cardiovascular disease) and the
preferred combinations of epilepsy treatments employed with
eslicarbazepine acetate are also planned.[4]

"We are collating data from over 17 real-world patient registries
and clinical studies sponsored by Eisai and BIAL to provide a single
source of information. The data will improve our knowledge and
understanding around the use of eslicarbazepine acetate in routine
clinical practice and the benefits this treatment may provide for
people with focal epilepsy," comments Patrício Soares-da-Silva,
Director of Research & Development, BIAL, Porto, Portugal.

Other data presented at this year's ECE included results from a
one-year retrospective observational study. The 'EARLY-ESLI study',
included 253 patients aged >=18 with partial-onset seizures who
failed on a first line monotherapy.[5] Patients received
eslicarbazepine acetate as an adjunctive treatment. The main reason
for initiating eslicarbazepine acetate was poor seizure control
(62.3%), adverse events with other anti-epileptic drugs (29.2%), and
compliance problems (8.3%). The one-year retention rate was 92.9%.[5]

At 12 months, 62.3% of patients were seizure-free for the last six
months. 31.6% of the patients reported adverse events (somnolence;
8.7%, dizziness; 5.1%, hyponatraemia; 3.5%) and along the follow-up,
3.6% discontinued treatment for that reason. In total, 127 patients
(50.2%) converted (withdrew) to monotherapy for at least 6 months.[5]

Eslicarbazepine acetate is already available in Albania*, Austria,
Czech Republic, Cyprus*, Denmark, Finland, France, Germany
(co-promotion with BIAL, the developer of eslicarbazepine acetate),
Greece, Iceland, Italy, Malta*, Norway, Portugal*, Republic of
Ireland, Russia***, Scotland, Slovakia, Sweden, Spain (co-promotion
with BIAL), UK (co-promotion with BIAL) and the U.S and Canada**.

*Exclusively by BIAL

**Eslicarbazepine acetate is sold in the U.S. and Canada under the
trade name Aptiom®

***Exalief® is the trade name for eslicarbazepine acetate in
Russia

Notes to Editors

About Zebinix® (eslicarbazepine acetate)

Eslicarbazepine acetate is currently marketed in Europe and Russia
by BIAL and by BIAL´s licensee, Eisai Europe Limited, a European
subsidiary of Eisai Co., Ltd. under the trade name Zebinix® or
Exalief®. 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 a voltage-gated sodium channel blocker.
It selectively targets the slow inactivated state of the sodium ion
channel (which have been implicated in the pathogenesis of epilepsy),
preventing its return to the active state, and thereby reduces
repetitive neuronal firing.[6] Further, eslicarbazepine acetate does
not inhibit potassium efflux, which may reduce the potential for
repetitive neuronal firings.[7] The efficacy of eslicarbazepine
acetate was demonstrated in an initial proof-of-concept phase II
study[8] and three subsequent phase III randomised, placebo
controlled studies in 1,049 people with refractory partial onset
seizures.[9],[10],[11]

About Epilepsy

Epilepsy is one of the most common neurological conditions in the
world, affecting approximately 6 million people in Europe, and an
estimated 50 million people worldwide.[12],[13] Epilepsy is a chronic
disorder of the brain that affects people of all ages. It is
characterised by abnormal discharges of neuronal activity which
causes seizures. Seizures can vary in severity, from brief lapses of
attention or jerking of muscles, to severe and prolonged convulsions.
Depending on the seizure type, seizures may be limited to one part of
the body, or may involve the whole body. Seizures can also vary in
frequency from less than one per year, to several per day. Epilepsy
has many possible causes but often the cause is unknown.

About BIAL

Founded in 1924, BIAL is an international pharmaceutical company
with the mission to discover, develop and provide therapeutic
solutions within the area of health. In recent decades, BIAL has
focused on quality, innovation and internationalisation.

Being the partner of choice for many companies, BIAL is strongly
committed to therapeutic innovation, investing more than 20% of its
turnover in Research and Development (R&D) every year.

BIAL has established an ambitious R&D programme centred on the
central nervous, cardiovascular system and allergy immunotherapy.
BIAL's innovative programmes focus on continuing the clinical
development of its anti-epileptic Zebinix®/Aptiom® (on the market in
Europe and the USA), as well as opicapone for Parkinson's disease.

The company expects to introduce more new medicines and vaccines
to the market in the next years, strengthening its position worldwide
and accomplishing the company's purpose of "Caring for your Health."

For more information about BIAL, please visit http://www.bial.com.

About Eisai Co., Ltd.

Eisai Co., Ltd. is a leading global research and development-based
pharmaceutical company headquartered in Japan. We define our
corporate mission as "giving first thought to patients and their
families and to increasing the benefits health care provides," which
we call our human health care (hhc) philosophy. With over 10,000
employees working across our global network of R&D facilities,
manufacturing sites and marketing subsidiaries, we strive to realise
our hhc philosophy by delivering innovative products in multiple
therapeutic areas with high unmet medical needs, including Oncology
and Neurology.

As a global pharmaceutical company, our mission extends to
patients around the world through our investment and participation in
partnership-based initiatives to improve access to medicines in
developing and emerging countries.

For more information about Eisai Co., Ltd., please visit
http://www.eisai.com

References

1. Ben-Menachem E, et al. Efficacy of eslicarbazepine acetate
versus controlled-release carbamazepine as monotherapy in patients
with newly diagnosed partial-onset seizures; European Congress on
Epileptology 2016: Abstract #0002

2. Zebinix® (eslicarbazepine acetate) SPC - Available at: http:
//www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Inform
ation/human/000988/WC500047225.pdf [updated 19th May 2016]. Accessed
September 2016

3. Trinka E, et al. Safety and tolerability of eslicarbazepine
acetate as monotherapy in patients with newly diagnosed partial-onset
seizures; European Congress on Epileptology 2016: Abstract #P615

4. McMurray R, et al. Effectiveness of eslicarbazepine acetate
as adjunctive therapy for partial epilepsy in clinical practice:
design of a European pooled analysis of real-world data; European
Congress on Epileptology 2016: Abstract #P578

5. Villanueva V, et al. EARLY-ESLI study: From early add-on to
monotherapy with eslicarbazepine acetate; European Congress on
Epileptology 2016: Abstract #0034

6. Hebeisen S, et al. Eslicarbazepine and the enhancement of
slow inactivation of voltage-gated sodium channels: a comparison with
carbamazepine, oxcarbazepine and lacosamide. Neuropharmacology 2015;
89:122-35

7. Soares-da-Silva P, et al. Eslicarbazepine acetate for the
treatment of focal epilepsy: an update on its proposed mechanisms of
action. Pharmacol Res Perspect. 2015; 3:e00124

8. Elger C, et al. Eslicarbazepine acetate: A double-blind,
add-on, placebo-controlled exploratory trial in adult patients with
partial-onset seizures. Epilepsia 2007; 48:497-504

9. Elger C, et al. Efficacy and safety of eslicarbazepine
acetate as adjunctive treatment in adults with refractory
partial-onset seizures: A randomised, double-blind,
placebo-controlled, parallel-group phase III study. Epilepsia.
2009;50:454-63

10. Ben-Menachem E, et al. Eslicarbazepine acetate as
adjunctive therapy in adult patients with partial epilepsy. Epilepsy
Res. 2010;89(2-3):278-85

11. Gil-Nagel A, 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;
120:281-87

12. Epilepsy in the WHO European Region: Fostering Epilepsy
Care in Europe. Available at:
http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf
Accessed September2016

13. Pugliatti M, et al. Estimating the cost of epilepsy in
Europe: A review with economic modeling. Epilepsia
2007:48(12):2224-33

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

Contact:
BIAL
Susana Vasconcelos
+351 229866100 / +351 229866148
Susana.Vasconcelos@bial.com Eisai
Cressida Robson / Ben Speller
+44 7908 314 155 / +44 7908 409 416 Ccressida_Rrobson@eisai.net/
Ben_Speller@eisai.net

Tonic Life Communications
Carys Thomas Ampofo / Chris Caudle
+44 7973 821 113 / + 44 7958 585 406
Carys.Thomas-Ampofo@toniclc.com/ Chris.Caudle@toniclc.com