Press Briefing, 30 May 2016, Bella Center, Copenhagen, Denmark
Three presentations on partial onset (focal) epilepsy treatment were held for members of the press at the 2nd Congress of the European Academy of Neurology (EAN) in Copenhagen, Denmark on 30th May 2016. The first presenter, Jukka Peltola, Consultant Neurologist and Deputy Chief Physician at the Tampere University Hospital in Finland, introduced epilepsy as one of the most common neurological conditions, with no age, ethnic, social class, or geographic boundaries.(1) The most common epilepsy seizure type experienced are focal seizures, which originate within networks limited to one brain hemisphere. Generalised seizures by contrast originate at some point within and rapidly engaging bilaterally distributed networks. Despite many available treatment options, management and control of seizures continues to be a challenge, with around one-third of patients considered to have refractory epilepsy, indicating an important unmet need for new treatment options.(2) Seizure control is vital to improve quality of life, reduce stigma and social and educational impact and to minimize long-term complications. (3, 4) (5)
A major goal of epilepsy management is to achieve seizure freedom with minimal side effects. (4) While the effectiveness of an antiepileptic drug (AED) is likely to be a combination of endpoints such as efficacy assessments (seizure freedom and responder rates), tolerability and quality of life assessments where available, to a person living with epilepsy, the AED effectiveness is a measure of “maintenance of a normal life”. This can be considered a combination of efficacy and tolerability of treatment. Adherence to treatment is a critical issue since non-adherence can have serious or fatal consequences, including motor vehicle accidents.(6)
New data on the role of eslicarbazepine acetate (ESL) in monotherapy treatment of partial onset (focal) seizures, were presented by Eugen Trinka, Professor and Chair from the Christian Doppler Klinik, Salzburg, Austria. ESL is a once-daily AED approved and marketed in Europe as adjunctive therapy in adults with partial onset seizures, with or without secondary generalization. In Phase II and III clinical trials, the majority adverse events were mild to moderate in intensity.(7-11) Treatment-emergent adverse events affecting more than 10% of patients were dizziness, somnolence and headaches. (7-11) Phase III data from a non-inferiority study in 815 newly diagnosed adults with partial inset seizures to investigate once daily ESL (800 to 1600 mg/daily) versus twice-daily controlled-release carbamazepine (CBZ-CR, 400 to 1200 mg/daily) were presented for the first time at EAN.(12, 13) At 26 weeks, 71.1% of patients receiving ESL and 75.6% receiving CBZ-CR were seizure free (average risk difference, –4.28%, 95% confidence interval, –10.3, 1.74%), indicating that ESL once-daily was non-inferior to CB-CR twice daily in this patient group. Treatment-emergent adverse events were similar between the two groups (ESL 75.3% versus CBZ-CR, 77.7%). The most frequently reported (>5% of all patients) adverse events possibly related to treatment are shown in Table 1. These results show that ESL represents a potential new monotherapy with a good efficacy, safety and tolerability profile.
ESL safety data from 6 years post-marketing sources were in accordance with cumulative experience during clinical development, according to pooled safety data presented on information obtained from health authorities, medical literature, spontaneous reports and non-interventional studies.(14) Data were obtained from 22 countries, mostly in Europe and the US, explained the presenter, Rui Sousa, Global Medical Affairs Manager, BIAL, Porto, Portugal. The estimated cumulative patient exposure up to 21 October 2015 was 1 109 657 patient months; 702 serious and 1272 non-serious adverse drug reactions from the various sources were reported, these included 47 serious adverse drug reactions from post-marketing non-interventional studies (Tables 2 and 3). Based on this available information the favourable benefit–risk profile of ESL remains unchanged from that indicated by clinical trials.
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7. Elger C, Bialer M, Cramer JA, Maia J, Almeida L, Soares-da-Silva P. 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, Halasz P, Maia J, Almeida L, Soares-da-Silva P. 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. Halasz P, Cramer JA, Hodoba D, Czlonkowska A, Guekht A, Maia J, et al. Long-term efficacy and safety of eslicarbazepine acetate: results of a 1-year open-label extension study in partial-onset seizures in adults with epilepsy. Epilepsia. 2010;51(10):1963-9.
10. Ben-Menachem E, Gabbai AA, Hufnagel A, Maia J, Almeida L, Soares-da-Silva P. Eslicarbazepine acetate as adjunctive therapy in adult patients with partial epilepsy. Epilepsy Res. 2010;89(2-3):278-85.
11. Sperling J, Harvey, A., Biraben, C., Galimberti,P., Kowacs,S.B.. Hong, H.., Cheng, D.., Blum, T.., Nunes, T., Soares-da-Silva, P. Adjunctive Eslicarbazepine Acetate In Patients With Refractory Partial-Onset Seizures: Efficacy Results Of A 12 Week Randomized Placebo-Controlled Study On Behalf Of The 304 Study Team/M. Sperling,. American Epilepsy Society Annual Meeting; 9 December; Washington, DC, UDA2013.
12. Trinka EK, P., Ben-Menachem, E., Elger, J. Moreira, C., Pinto, R., Ikedo, F., Pereira, A., Rocha, J.F. Soares-da-Silva, P. Efficacy of eslicarbazepine acetate versus controlled-release carbamazepine as monotherapy in patients with newly diagnosed partial-onset seizures. European Academy of Neurology (EAN); 30 April; Bella Centre, Copenhagen, Denmark2016.
13. Kowacs P, Trinka, E., Ben-Menachem, E., Elger, C., Moreira, J., Pinto, R. ,Ikedo, F., Pereira, A., Rocha, J.F., Soares-da-Silva, P.,. Safety and tolerability of eslicarbazepine acetate as monotherapy in patients with newly diagnosed partial-onset seizures. European Academy of Neurology (EAN); 30 April; Bella Centre, Copenhagen, Denmark2016.
14. Vieira M, Gama, H., Graça, J., Costa, R., Sousa, R., Soares-da-Silva, P. Eslicarbazepine acetate: update of post-marketing safety data. European Academy of Neurology (EAN); 30 April; Bella Centre, Copenhagen, Denmark2016.
Table 1. Most frequently reported (>5% of all patients) possible treatment-emergent adverse events with esclicarbazepine acetate versus controlled-release carabamazepine in a Phase III study in patients with newly diagnosed partial-onset seizures.(13)
ESL, eslicarbazepine acetate; CBZ-CR, controlled-release carbamazepine
Table 2. Most common adverse drug reactions with eslicarbazepine acetate treatment, from post-marketing safety data. (14)
Table 3. Most common reported adverse drug reaction terms with eslicarbazepine acetate treatment, from post-marketing safety data (14)