Data Presented at 12th European Congress on Epileptology (ECE) Offers New Insights into Seizure Control and Safety Profi

PORTO, Portugal and HATFIELD, England, September 13, 2016 /PRNewswire/ --

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

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

practice 

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.[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 (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.[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 (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.[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 greater than or equal to18 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(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.[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   

(CONTINUA)