PORTO, Portugal and HATFIELD, England, September 13, 2016 /PRNewswire/ --
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Methodology also announced for large pan-European pooled analyses of Zebinix(R) (eslicarbazepine acetate) real-world data to assess use for partial epilepsy in clinical
Data from an investigational Phase III study for adjunctive Zebinix(R) (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. Eslicarbazepine acetate is currently indicated in Europe as adjunctive therapy in adults with partial onset seizures, with or without secondary generalisation.
The non-inferiority study included 785 eligible patients (greater than or equal to18 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.
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%).
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%).
"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. 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 (greater than or equal to50% 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.
"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 greater than or equal to18 with partial-onset seizures who failed on a first line monotherapy. 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%.
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.
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(R)
***Exalief(R) is the trade name for eslicarbazepine acetate in Russia
Notes to Editors
About Zebinix(R) (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(R) or Exalief(R). In the United States and Canada eslicarbazepine acetate (tradename Aptiom(R)) 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. Further, eslicarbazepine acetate does not inhibit potassium efflux, which may reduce the potential for repetitive neuronal firings. The efficacy of eslicarbazepine acetate was demonstrated in an initial proof-of-concept phase II study and three subsequent phase III randomised, placebo controlled studies in 1,049 people with refractory partial onset seizures.,,
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. , 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.
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(R)/Aptiom(R) (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 [https://webmail.hhealth.com/owa/redir.aspx?C=6OjkkH_Oz0KcpqZqtz0gYu5W64yst9IIliR8UZVYwgaeouwuOzC4BDQV-nJBoz6bpw7MInczpyk.&URL=http%3a%2f%2fwww.eisai.com%2f ]
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(R) (eslicarbazepine acetate) SPC - Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/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
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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
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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
CONTACT: BIAL, Susana Vasconcelos, +351 229866100 / +351 229866148,Susana.Vasconcelos@bial.comEisai, Cressida Robson / Ben Speller, +44 7908 314 155 / +44 7908 409 416Ccressida_Rrobson@eisai.net Ben_Speller@eisai.net ; Tonic LifeCommunications, Carys Thomas Ampofo / Chris Caudle, +44 7973 821 113 / + 447958 585 406, Carys.Thomas-Ampofo@toniclc.com Chris.Caudle@toniclc.com