Phase III Clinical Data Show Zebinix® (Eslicarbazepine Acetate) to Be Effective and Well Tolerated in Elderly

HATFIELD, England, May 26, 2015 /PRNewswire/ --

PRESS RELEASE FOR EU MEDIA ONLY: NOT FOR SWISS/AUSTRIAN/U.S JOURNALISTS 

Data for once-daily, novel anti-epileptic drug Zebinix^® (eslicarbazepine acetate) shows it to be effective and well tolerated in elderly people with partial onset seizures (POS), with a 54% decrease in seizure frequency from baseline observed over the maintenance period of the study.^[1] These data will be presented in full at the Association of British Neurologists Annual Meeting in Harrogate, United Kingdom, 20-22 May 2015 (abstract no.017).

Old age is the most common time to develop epilepsy^[2] and treatment of this age group remains a challenge due to the high presence of co-morbidities and the need for polypharmacy. Seizure control and reduction of side effects are key treatment goals.^[2]

Results from the Phase III study, which evaluates the safety and efficacy of eslicarbazepine acetate as adjunctive therapy in elderly patients aged ≥65 years with POS, do not raise any major safety concerns.^[1] Of the 72 participants included in the study, 47 (65%) experienced 152 treatment-emergent adverse events. These results are consistent with those previously reported for eslicarbazepine acetate and the side effects were consistent with the known profile of eslicarbazepine acetate.

The seizure frequency observed over the maintenance period (seizure frequency/four weeks) is shown to decrease from 2.9 at baseline to 1.2, a median change of -54.1%. During the treatment period, 11 (15.5%) subjects were seizure-free and a total of 39 (54.9%) subjects were responders (50% or greater reduction of seizure frequency relative to baseline).^[3]

"These data are of interest as the management of side effects of epilepsy treatments in older people can be complicated. The safety and efficacy profile of eslicarbazepine acetate in this study should convince doctors to take a renewed look at the treatment regime to offer elderly patients and offer a sound replacement for older anti-epilepsy drugs traditionally used in this age group," commented Professor Soares da Silva, Director of the R&D Department at BIAL.

Eslicarbazepine acetate is indicated as adjunctive therapy in adults with partial onset seizures, with or without secondary generalisation.^[4] The oral, once-daily dose therapy has a short and simple titration to target dose for seizure control.

"Eisai is committed to the therapeutic area of epilepsy. Studies in an elderly population such as this one are important as treatment needs may differ to those of a younger person with epilepsy. Solutions that will help people with epilepsy, their families and carers is at the centre of what we do," commented Mike Bee, Epilepsy Business Unit Director, Eisai EMEA.

The continued development of eslicarbazepine acetate underscores Eisai's human health care (hhc) mission, the company's commitment to innovative solutions in disease prevention, cure and care for the health and wellbeing of people worldwide. Eslicarbazepine acetate is already available in Albania*, Austria, Czech Republic, Cyprus*, Denmark, England, Finland, France, Germany, Greece, Iceland, Malta*, Norway, Portugal*, Republic of Ireland, Russia, Scotland, Sweden, Finland, Spain (co-promotion with BIAL, the developer of eslicarbazepine acetate), Wales, Canada, and the U.S**.

*Exclusively by BIAL

**Eslicarbazepine acetate is sold in the U.S. under the trade name APTIOM^®

Notes to Editors 

About the safety and efficacy of eslicarbazepine acetate in elderly patients study^[1]

This Phase III, multicentre, open-label, non-controlled study assesses the safety/tolerability and efficacy of eslicarbazepine acetate as adjunctive therapy in patients aged ≥65 years with ≥2 POS during an 8-week baseline and treated with 1-2 antiepileptic drugs. Following baseline, patients entered a 26-week maintenance period. Eslicarbazepine acetate was initiated at 400 mg once-daily and adjusted (400-1200 mg/day) based on individual response. Safety/tolerability evaluations included treatment-emergent adverse events (TEAEs), vital signs, 12-lead electrocardiogram and physical/neurological examinations [Norris' scales for evaluation of sedative effects and Columbia Suicide Severity Rating Scale (C-SSRS)]. Efficacy evaluations included change in standardised seizure frequency (SSF; seizure frequency/4 weeks), the proportion of seizure-free subjects, responder rate, number of days with seizures, and Patient Global Impression of Change (PGIC).

Of the 72 patients included, 47 (65.3%) experienced 152 TEAEs; most commonly, dizziness (12.5%), somnolence (9.7%), fatigue (8.3%), convulsion (8.3%) and hyponatraemia (8.3%). Three patients died of cardiac failure, glioblastoma multiforme and ischaemic stroke (relationship unlikely/not related). Overall, 16 (22.2%) patients discontinued due to TEAEs. Incidence of clinically significant findings was low for vital signs, electrocardiogram and physical/neurological examinations. SSF decreased from 2.9 at baseline to 1.2 during the maintenance period (median relative change: -54.1%).

About Zebinix^®(eslicarbazepine acetate)

Eslicarbazepine acetate is a voltage-gated sodium channel blocker.^[5] The molecule interacts competitively with the inactive state of the sodium ion channel^[4],[6] preventing its return to the active state, and thereby inhibiting repetitive neuronal firing.^[4]The efficacy of eslicarbazepine acetate was demonstrated in an initial proof-of-concept phase II study^[7] and three subsequent phase III randomised, placebo controlled studies in 1049 adult patients with refractory partial onset seizures^[8],[9],[10]

For further information please visit: http://www.eisai.co.uk

Zebinix^® is the EU trade name for eslicarbazepine acetate

Zebinix^® is under license from BIAL

About Eisai EMEA 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, Russia and Oceania (EMEA).

In the EMEA region, Eisai currently has four marketed treatments including:

• 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
• Inovelon^® (rufinamide) for the adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome in patients >4 years. (Rufinamide was originally developed by Novartis)
• Zebinix^® (eslicarbazepine acetate) as adjunctive therapy in adult patients with partial onset seizures, with or without secondary generalisation. (Zebinix is under license from BIAL)
• Zonegran^® (zonisamide) as monotherapy in adults and adjunctive therapy in adults, adolescents and children aged six years and above with partial onset seizures, with or without secondary generalisation. (Zonegran is under license from the originator Dainippon Sumitomo Pharma)

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.  

About BIAL  

Founded in 1924, BIAL's mission is to discover, develop and provide therapeutic solutions within the area of health. In recent decades, BIAL has focused on quality, innovation and internationalization. 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 several French- or Portuguese-speaking African countries.

BIAL is strongly committed to therapeutic innovation, investing more than 20% of its turnover in research and development (R&D) every year, placing it among the most innovative European companies. Key research areas for BIAL are the central nervous system, the cardiovascular system and allergen 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.

With a team of 900 employees, BIAL has reinforced its international presence, an aspect that the company will strengthen over the next decade.

Further information about BIAL can be found at http://www.bial.com

References 

1. Costa R et al. Safety and efficacy of eslicarbazepine acetate in elderly patients. Association of British Neurologists annual meeting 2015; Abstract #017 

2. Brodie M et al. Epilepsy in elderly people. BMJ 2005;331(7528):1317-1322. 

3. Eisai. Data on file. 2015 

4. Zebinix , Summary of Product Characteristics (updated November 2014): http://www.medicines.org.uk/emc/medicine/22376/

5. Almeida L et al (BIA 2-093). Neurotherapeutics 2007;4(1):88-96 

6. Elger C et al. Pharmacokinetics and tolerability of eslicarbazepine acetate and oxcarbazepine at steady state in healthy volunteers. Epilepsia 2013;54(8):1453-61. 

7. Elger 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 

8. Elger C 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):454-63. 

9. Ben-Menachem E et al. Eslicarbazepine acetate as adjunctive therapy in adult patients with partial epilepsy; Epilepsy Research 2010;89:278-85. 

10. 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. 

Date of preparation: May 2015 
Job code: Perampanel-UK2189