Zebinix® (eslicarbazepine acetate) New Six-year Post-marketing Data Shows Safety Profile is Unchanged as 'Real-world' Study Results are Presented for First Time at the Second Congress of the European Academy of Neurology (EAN) 2016, Copenhagen

PORTO, Portugal and HATFIELD, England, May 31, 2016 /PRNewswire/ --

PRESS RELEASE FOR EU MEDIA ONLY: NOT FOR AUSTRIAN/SWISS/US JOURNALISTS 

Bial and Eisai also announces for first time in Europe phase III data showing once-daily eslicarbazepine acetate is as effective and well-tolerated as twice-daily controlled-release carbamazepine^[2],[3] 

Zebinix^® (eslicarbazepine acetate) safety is unchanged in the 'real-world', with data comparable to clinical trials, according to a Bial-sponsored post-marketing surveillance analysis reviewing the cumulative exposure of over one million patients-months worldwide.^[1] Eslicarbazepine acetate is currently indicated in Europe as adjunctive therapy in adults with partial onset seizures, with or without secondary generalisation.^[4]

Bial and Eisai are announcing the data for the first time at the Second Congress of the European Academy of Neurology (EAN) 2016, Copenhagen. Other pivotal data^[2],[3] being presented at EAN and for the first time in Europe show that treatment with once-daily eslicarbazepine acetate monotherapy is as effective as twice-daily controlled-release carbamazepine, a standard of care, and is well-tolerated.

"Partial-onset or focal seizures are the most frequent type and confirmation that six year real world data for a treatment aligns with the clinical trials is reassuring," comments Jukka Peltola, Neurologist, Department of Neurology, Neurosurgery and Rehabilitation, Tampere University Hospital, Finland.

The post-marketing pharmacovigilance analysis^[1] assesses the safety of eslicarbazepine acetate. These data, reporting up to October 2015, now show six years' comparable safety to the clinical trials that underpinned the marketing authorisation^[4], with an estimated cumulative patient exposure of over one million patients-months (1,109,656)^[1]. There are reports of 702 serious and 1,273 non-serious ADRs from health authorities, literature and spontaneous reports, and 47 serious ADRs from post-marketing non-interventional studies. The three most common serious ADRs are nervous system disorders (240), metabolism and nutrition disorders (177) and skin and subcutaneous tissue disorders (121).

"These results underline our commitment to developing and delivering beneficial treatment options for people living with epilepsy," comments Patrício Soares-da-Silva, Head of Research & Development, Bial.

Other pivotal Phase III Bial-sponsored data presented at EAN and for the first time in Europe show that seizure freedom rates with eslicarbazepine acetate are similar to that of controlled-release carbamazepine ie; (71.1% versus 75.6%) in 785 eligible patients at ≥6 months at the last evaluated dose (average risk difference -4.28%, 95%CI -10.3, 1.74%).  The one-year seizure-free rate at the last evaluated dose was 64.7% in the eslicarbazepine acetate group and 70.3% in the controlled-release carbamazepine group (average risk difference: -5.46%; 95%CI: -11.88, 0.97%).^[2]

For safety analysis^[3] in 813 patients, eslicarbazepine acetate is well tolerated and side effects are mild to moderate. Incidence rates of treatment emergent adverse events (TEAEs) were similar but slightly lower in patients receiving eslicarbazepine acetate versus patients receiving controlled-release carbamazepine (75.3% vs 77.7% respectively). Possibly-related TEAEs for eslicarbazepine acetate were 43.6% compared with 51.5% for controlled release carbamazepine.  Serious treatment-related TEAEs in eslicarbazepine acetate treated patients versus patients treated with controlled release carbamazepine were 2.0% vs 2.7% and for TEAEs leading to withdrawal were 13.5% vs 18%.The most frequently reported possibly-related TEAEs for eslicarbazepine acetate were headache, dizziness, nausea, fatigue, and somnolence.^[3]

"These data show the efficacy of eslicarbazepine acetate as a monotherapy, as 71% of people are seizure-free for six consecutive months. They also demonstrate that eslicarbazepine acetate has a similar efficacy and safety profile to controlled-release carbamazepine and we hope that it may be a treatment option for patients in the future," comments Eugen Trinka, Professor and Chair of the Department of Neurology, Paracelsus Medical University, Salzburg, Austria.

The study^[2],[3] is a randomised, double-blind, parallel-group, active-controlled and non-inferiority study, investigating the efficacy and safety of once-daily eslicarbazepine acetate (800 to 1600 mg/daily) as monotherapy treatment for newly diagnosed adults (18 years and older) with partial-onset seizures in comparison with twice-daily controlled-release carbamazepine (400 to 1200 mg/daily).  The primary endpoint is the proportion of people seizure free for the entire 26-week evaluation period.  Secondary endpoints include the time to first seizure, a QOLIE-31 quality of life assessment, and safety. The study examines data for newly diagnosed people, aged 18 and over, with epilepsy who experience partial-onset seizures, to evaluate eslicarbazepine acetate as a single treatment option (815 patients for efficacy and 813 for safety analyses).

The continued development of eslicarbazepine acetate underscores Bial and Eisai's commitment in optimizing the treatment care of patients with epilepsy. 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^®

Notes to Editors  

About Zebinix^® (eslicarbazepine acetate)

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 currently indicated in Europe as adjunctive therapy in adults with partial onset seizures, with or without secondary generalisation.^[4] In the US, eslicarbazepine acetate (Aptiom®) is indicated for the treatment of partial-onset seizures as monotherapy or adjunctive therapy.^[5]

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]}

• Zebinix^® is the EU trade name for eslicarbazepine acetate
• Zebinix^® is under license from BIAL
• Aptiom^® is the trade name for eslicarbazepine acetate in the U.S. and Canada and is under license to Sunovion Pharmaceuticals Inc.

About Epilepsy  

Epilepsy is one of the most common neurological conditions in the world, affecting approximately six million people in Europe, and an estimated 50 million people worldwide.^[12] 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 program 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. Vieira M, et al. Eslicarbazepine acetate: update of post-marketing safety data. Presented at EAN 2016; abstract # P32053

2. Trinka E, et al. Efficacy of eslicarbazepine acetate versus controlled-release carbamazepine as monotherapy in patients with newly diagnosed partial-onset seizures. Presented at EAN 2016; abstract # P31067

3. Kowacs P, et al. Safety and tolerability of eslicarbazepine acetate as monotherapy in patients with newly diagnosed partial-onset seizures.  Presented at EAN 2016; abstract # P32045

4. Zebinix® SPC (updated 23 June 2015).  Available at: https://www.medicines.org.uk/emc/medicine/22376/SPC/Zebinix+800mg+tablets/ Accessed April 2016

5. Food and Drug Administration, Highlights of Prescribing Information https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022416s001lbl.pdf (accessed May 2016)

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

Date of preparation: May 2016
Job code: Zebinix-UK2404