Clinical trial results for new epilepsy treatment Keppra (levetiracetam) reported at 6th European Paediatric Neurology Society C

Main Category: Epilepsy
Article Date: 18 Sep 2005 - 13:00 PDT

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Paediatric clinical trial results of the new epilepsy treatment Keppra (levetiracetam) were reported in Europe for the first time, at this week's meeting of the 6th European Paediatric Neurology Society Congress hosted in Sweden. Data indicate that levetiracetam adjunctive therapy provides enhanced seizure freedom over placebo, and is well-tolerated in children with partial epilepsy who have been resistant to anti-epileptic (AED) therapy1.

"More than 25% of children with epilepsy experience treatment resistant seizures or intolerable side effects from medication" said Tracy Glauser, M.D., director of the Comprehensive Epilepsy Program, Cincinnati Children's Hospital and principal investigator of the study. "Keppra was effective and well-tolerated by children in the study, many of whom had tried multiple anti-epileptic drugs prior to trying Keppra."

Results presented were from a multicentre, double-blind, randomized, placebo-controlled study in 198 children (4-16 years), with partial onset seizures with or without secondary generalisation uncontrolled by standard AEDs. Results show that 45% of those who received levetiracetam at a target dose of 60 mg/kg/day for 14 weeks had at least a 50% reduction in seizure frequency, and 7% became seizure free.1 This compared with 19% (p=0.0002) and 1% respectively in placebo-treated patients. Prior to treatment with levetiracetam, the children in the study were experiencing approximately five seizures per week (median = 4.7 and 5.3 for the levetiracetam and placebo group respectively) despite treatment with 1-2 other AEDs.1

Levetiracetam was well tolerated, and fewer children withdrew from treatment because of adverse events compared to the placebo group (5% and 9% withdrawal for the levetiracetam and placebo group, respectively)1. With the exception of somnolence (22.8% and 11.3% for the levetiracetam and placebo group, respectively), the incidence of treatment related adverse events was similar between patients in the levetiracetam and placebo groups with the most commonly reported treatment adverse events being somnolence, infection, accidental injury, vomiting and headache1

. In August 2005, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) issued a positive opinion, recommending approval of Keppra as adjunctive therapy in the treatment of partial-onset seizures, with or without secondary generalisation, in children four years of age and older with epilepsy.

In the US, Keppra (leveitracetam) is indicated as adjunctive therapy in the treatment of partial onset seizures in adults and children four years of age and older with epilepsy. In adults, Keppra use is associated with the occurrence of central nervous system adverse events including somnolence and fatigue, coordination difficulties, and behavioral abnormalities, as well as hematological abnormalities. In adults, the most common adverse events associated with Keppra in combination with other AEDs are somnolence, asthenia, infection, and dizziness. Of these, most appeared to occur predominantly during the first 4 weeks of treatment. In pediatric patients 4 to16 years of age, the most common adverse events associated with Keppra in combination with other AEDs are somnolence, accidental injury, hostility, nervousness, and asthenia.

In Europe, Keppra (levetiracetam) is indicated as adjunctive therapy in the treatment of partial onset seizures with or without secondary generalisation, in patients over 16 years of age. In August 2005 the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) issued a positive opinion, recommending approval for registration of Keppra as adjunctive therapy in the treatment of partial-onset seizures, with or without secondary generalisation, in children four years of age and older with epilepsy. This positive opinion is currently under consideration by the European Commission.

Monotherapy study

This week, UCB also announced that Keppra is as effective as standard therapy as a first-line monotherapy for epileptics with partial or generalised tonic-clonic seizures, according to results from the company's pivotal Phase III monotherapy clinical trial.

The study results indicate that Keppra is as effective as sustained-release carbamazepine, the most widely prescribed drug for this type of epilepsy, in keeping patients seizure-free. The trial compared Keppra (levetiracetam) to sustained release carbamazepine in newly diagnosed patients, suffering from epilepsy with partial or generalised tonic-clonic seizures. "Keppra emerged from this study as the first of the new generation anti-epileptic drugs to show non-inferiority to sustained release carbamazepine with six month seizure freedom rates of 73.0% and 72.8% for the Keppra and carbamazepine groups, respectively" said Professor Emilio Perucca, Lead Trial Investigator, University of Pavia, Italy.

UCB plans to file a marketing authorization application with the EMEA for the use of Keppra as monotherapy in patients with epilepsy and also plans to review the data with the US Food and Drug Administration (FDA).

Written by - Ian Mason

References

1. Lu Z, Glauser TA, Ayala R, Elterman RD, Mitchell WG, Van Orman CB, Gauer LJ Levetiracetam adjunctive therapy in children with refractory partial epilepsy, in comparison with other new anti-epileptic drugs. Poster Presentation at the 6th European Paediatric Neurology Society Congress, Goteborg, September 2005.

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