New European real-world audit data provides additional information on the effectiveness of Zebinix® (eslicarbazepine acetate) for the treatment of partial-onset epilepsy in adults

PORTO, Portugal and HATFIELD, England, December 12, 2017 /PRNewswire/ --

• Results from the pooled analysis presented at the American Epilepsy Society Annual Meeting 2017 in Washington DC, US.^[1],[2],[3]  

Bial and Eisai have announced new real-world audit data presented at the American Epilepsy Society (AES) Annual Meeting 2017, which add to the existing clinical trials examining the effectiveness and tolerability of Zebinix^® (eslicarbazepine acetate). These data assess the real-world effectiveness, safety and tolerability of eslicarbazepine acetate when used as monotherapy in patients with partial-onset seizures, following conversion from previous treatment with carbamazepine or oxcarbazepine and when treated with ≤1200 or >1200 mg/day eslicarbazepine acetate.^[1],[2],[3]

Euro-Esli, an exploratory pooled analysis of data from 14 European clinical practice studies including 2,058 patients aged 14-88 years old with partial-onset seizures (POS), with or without secondary generalization, examined the real world use of eslicarbazepine acetate as monotherapy, as well as adjunctive therapy, for POS in clinical practice.

"Euro-Esli study offered data of >200 patients with eslicarbazepine acetate in monotherapy, where it proved to be an effective and tolerable option," says Dr Vicente Villanueva, Neurologist and Epileptologist, Hospital Universitario y Politécnico La Fe, Valencia, Spain.

The Euro-Esli study also showed that eslicarbazepine acetate was efficacious and generally well tolerated in patients switching from carbamazepine or oxcarbazepine in clinical practice.^[1] A further abstract, examining a different Euro-Esli data set, explored the effectiveness, safety and tolerability of eslicarbazepine acetate in patients with partial-onset seizures treated with ≤1200 or >1200 mg/day.^[2]

Epilepsy is one of the most common neurological conditions in the world, affecting approximately fifty million people in Europe. ^[4] It is defined as either: (1) the occurrence of two or more unprovoked seizures >24 hours apart; (2) one unprovoked (or reflex) seizure and a probability of further seizures occurring over the next 10 years that is similar to the general recurrence risk (at least 60%) after two unprovoked seizures; (3) diagnosis of an epilepsy syndrome.^[5] Depending on the type, seizures may involve one part of the body or the whole body, and may affect consciousness. Epilepsy has many possible causes but sometimes the cause is unknown.^[6]

"Real-world data explores the impact of a treatment in a real-life environment and these data improve our knowledge and understanding around the use of eslicarbazepine acetate, reinforcing BIAL's commitment to developing and delivering beneficial treatment options for people living with epilepsy." comments António Portela, CEO of BIAL.

"We are committed to the development of our anti-epileptic drug product portfolio, and Eisai continues to invest in real world evidence which will help us ensure we are addressing the diversity of epilepsy patients, which may help improve their quality of life," comments Neil West, Vice President EMEA, Global Neurology Business Unit at Eisai.

In Europe eslicarbazepine acetate is indicated as:

• monotherapy in the treatment of partial-onset seizures, with or without secondary generalisation, in 
  adults with newly diagnosed epilepsy;
• adjunctive therapy in adults, adolescents and children aged above 6 years, with partial-onset seizures with or without secondary generalisation.^[7]

Notes to Editors  

About the Euro-Esli study^[1],[2],[3]

Euro-Esli was a pooled analysis of 14 European clinical practice studies. Effectiveness assessments included responder rate (≥50% seizure frequency reduction) and seizure freedom rate (seizure freedom at least since prior visit), assessed after 3, 6 and 12 months of ESL treatment, and at last visit. Safety and tolerability were assessed throughout follow-up by evaluating adverse events (AEs) and ESL discontinuation due to AEs, respectively.

Monotherapy in clinical practice^[3]

Data were compared for patients treated initially with ESL monotherapy versus adjunctive therapy, and for patients treated at last visit with ESL monotherapy versus adjunctive therapy.  

Of the 2058 patients included in Euro-Esli (mean age 44.0 years; 52.1% male), the number of concomitant AEDs used at baseline and last visit was known for 2045 and 1340 patients, respectively. ESL was used as monotherapy in 88/2045 (4.3%) patients initially and in 229/1340 (17.1%) patients at last visit. At 12 months, responder and seizure freedom rates were significantly higher in patients treated initially with ESL monotherapy versus adjunctive therapy, and in patients treated at last visit with ESL monotherapy versus adjunctive therapy. The overall incidence of AEs was similar in patients treated initially with ESL monotherapy and adjunctive therapy, and in patients treated at last visit with ESL monotherapy and adjunctive therapy. The rate of discontinuation due to AEs was not significantly different in patients treated initially with ESL monotherapy versus adjunctive therapy, but the rate was significantly lower in patients treated at last visit with ESL monotherapy versus adjunctive therapy.  

Transitioning from carbamazepine or oxcarbazepine in everyday clinical practice^[1]

Data were analysed for cohorts of patients who transitioned from carbamazepine or oxcarbazepine to ESL either due to, in most of the cases, lack of efficacy or poor tolerability.

Euro-Esli included 2058 patients (52.1% male; mean age, 44 years; mean duration of epilepsy, 20.9 years), of whom 233 (11.3%) transitioned from carbamazepine to ESL and 134 (6.5%) transitioned from oxcarbazepine to ESL. After 12 months of ESL treatment, responder and seizure freedom rates for patients transitioning from carbamazepine due to lack of efficacy (n=163) were 70.0% and 30.9%, respectively. Corresponding values for patients transitioning from oxcarbazepine due to lack of efficacy (n=90) were 57.1% and 25.0%, respectively. Among patients who transitioned from carbamazepine and oxcarbazepine to ESL due to lack of efficacy, 11.6% and 10.5% discontinued ESL due to lack of efficacy, respectively. Among patients who transitioned from carbamazepine and oxcarbazepine to ESL due to poor tolerability (n=64 and n=61, respectively), 26.6% and 39.5% experienced AEs, and 8.3% and 6.8% discontinued ESL due to AEs, respectively.

Doses >1200 mg/day versus ≤1200 mg/day^[2]

Data were compared for patients who were treated at any time during follow-up with ESL at a dose >1200 mg/day vs those who were only treated with ESL at doses ≤1200 mg/day.

Of the 2058 patients included in Euro-Esli (mean age 44.0 years; 52.1% male), information on ESL dosing was known for 1920 patients. Among these patients, 1749 (91.1%) were treated with ESL ≤1200 mg/day and 171 (8.9%) were treated with ESL >1200 mg/day. The number of prior antiepileptic drugs used was significantly lower in patients treated with ESL ≤1200 vs >1200 mg/day (median, 3 vs 4; mean, 4 vs 5; p<0.001; Mann-Whitney test). At all timepoints, responder and seizure freedom rates were significantly higher in patients treated with ESL ≤1200 mg/day than in those treated with ESL >1200 mg/day. The overall incidence of AEs was significantly higher in patients treated with ESL ≤1200 mg/day vs >1200 mg/day (34.8% vs 22.8%; 2=9.91; p=0.002; Chi-squared test). Similarly, the rate of ESL discontinuation due to AEs was significantly higher in patients treated with ESL ≤1200 mg/day vs >1200 mg/day (14.7% vs 6.1%; 2=9.27; p=0.002; Chi-squared test).

About Zebinix^® (eslicarbazepine acetate)

Eslicarbazepine acetate is a voltage-gated sodium channel blocker, which selectively targets the slow inactivated state of the sodium ion channel.^[8] The efficacy of eslicarbazepine acetate was demonstrated in an initial proof-of-concept phase II study^[9] and three subsequent phase III randomised, placebo controlled studies in 1,049 people with refractory partial-onset seizures.^{[10],[11],[12]}

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.

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 strategically focused on quality, innovation, and internationalisation.

Bial is strongly committed to therapeutic innovation, investing more than 20 per cent of its turnover in Research and Development (R&D) every year.

Bial has established an ambitious R&D program centered on the neurosciences and cardiovascular system. The company expects to introduce more new medicines to the market in the next years, strengthening its international presence based in its own innovative medicines, and accomplishing the company's purpose of "Caring for your Health."

For more information about Bial, please visit 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 www.eisai.com.

References  

1. Peltola J, McMurray R, Villanueva V. (2017) Efficacy, safety and tolerability of eslicarbazepine acetate in patients transitioning from carbamazepine or oxcarbazepine in everyday clinical practice. American Epilepsy Society Annual Meeting (AES) 2017; Washington, US. Abst. 1.319. 

2. Villanueva V, McMurray R. (2017) Effectiveness, safety and tolerability of eslicarbazepine acetate at doses >1200 mg/day versus ≤1200 mg/day: real-world evidence from the Euro-Esli study. American Epilepsy Society Annual Meeting (AES) 2017; Washington, US. Abst. 1.318. 

3. McMurray R, Villanueva V, Delanty R. (2017) Real-world data on the effectiveness, safety and tolerability of eslicarbazepine acetate monotherapy in clinical practice. American Epilepsy Society Annual Meeting (AES) 2017; Washington, US. Abst. 2.313.  

4. Saxena S, et al. (2017) Defeating epilepsy: A global public health commitment. Epilepsia Open. 2 (2), 153-155. 

5. Fisher, R.S., et al. (2014) ILAE Official Report: A practical clinical definition of epilepsy. Epilepsia. 55(4), 475-482. 

6. Laxer D, et al. (2014) The consequences of refractory epilepsy and its treatment. Epilepsy & Behaviour. 37, 59-70. 

7. Eisai. (2017) Zebinix® (eslicarbazepine acetate) Summary of Product Characteristics. Available from: 

http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000988/WC500047225.pdf. [Accessed October 2017]. 

8. Hebeisen S, et al. (2015) Eslicarbazepine and the enhancement of slow inactivation of voltage-gated sodium channels: A comparison with carbamazepine, oxcarbazepine and lacosamide. Neuropharmacology. 89, 122-135 

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

10. Elger C, et al. (2009) 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. 50, 454-63. 

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

12. Gil-Nagel A, et al. (2009) Efficacy and safety of 800 and 1200 mg eslicarbazepine acetate as adjunctive treatment in adults with refractory partial-onset seizures. Acta Neurologica Scandinavica. 120, 281-87. 

December 2017
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