Epilepsy - eslicarbazepine acetate
Epileptics experience seizures as a result of electrical signalling problems in the brain. It is most common in children and the elderly. Drugs are used to control it, but in a third of patients the medicines do not work fully. Carbamazepine has been used to treat epilepsy since the 1960s; it acts by stabilising the inactivated state of the voltage gated sodium channels in the brain, rendering the neurons less excitable.
Epileptics experience seizures as a result of electrical signalling problems in the brain. It is most common in children and the elderly. Drugs are used to control it, but in a third of patients the medicines do not work fully. Carbamazepine has been used to treat epilepsy since the 1960s; it acts by stabilising the inactivated state of the voltage gated sodium channels in the brain, rendering the neurons less excitable.
Over the years alternatives have been introduced, some of which are based on it. Another of these that is under development, eslicarbazepine, is an active metabolite of another drug, oxcarbazepine, administered in prodrug acetate form.1 It was developed by Bial-Portela, and has been licensed to Eisai in Europe and Sepracor in North America.
A number of Phase III trials have been carried out on its use as an adjunctive therapy. In one double blind, placebo-controlled, parallel group multicentre study, 252 patients with refractory partial onset seizures were randomised to 800 or 1200mg of the drug or placebo for 12 weeks, after an eight week baseline period and then a two week period of half doses being given.2 Patients in both groups experienced significantly fewer seizures during the 12 week period than those given placebo, and the median relative reduction in seizure frequency was 38% for the lower dose group and 42% for the higher dose, compared with 17% in the placebo group. The most common adverse events were dizziness, somnolence, headache and nausea, all of which were of mild or moderate severity.
A similar dosing regime was also used in another study in patients with refractory partial seizures.3 It was given as an adjunct to existing therapy, with the most common concomitant drugs being carbamazepine, lamotrigine and valproic acid. Again, seizure frequency was significantly lower than placebo in both treatment groups, up to a 45% median relative reduction for the highest dosage group.
Similar efficacy results were seen in patients given the new drug both with and without carbamazepine. Higher doses gave higher discontinuation rates because of adverse events: from 3.9% for placebo through 8.3% for the 800mg group, and 19.6% in the 1200mg group.
The drug has now been given the go-ahead as a treatment for partial onset seizures as an add-on therapy by EMEA, and the US FDA has accepted it for filing.