Public Release: 

FDA approves new treatment for children with epilepsy

New indication for Lamictal® offers seizure control for young patients with partial seizures

GlaxoSmithKline

Research Triangle Park, NC (January 20, 2002) - GlaxoSmithKline announced today that the U.S. Food and Drug Administration (FDA) granted marketing clearance for Lamictal® (lamotrigine) Tablets as add-on therapy in partial seizures in children age two years old and up. This new indication expands the already-approved indications for adjunctive use in adults with partial seizures, and for the generalized seizures of Lennox-Gastaut Syndrome in children two years of age and older.

Partial seizures are the most common type of epilepsy, affecting approximately 70% of all people with the illness. Partial seizures begin with abnormal electrical activity in a particular location in the brain. Specific effects of this kind of seizure depend on the part of the brain involved, and may include a dazed state, lip smacking, or jerking movements of certain body parts. According to the Epilepsy Foundation, epilepsy affects 2.3 million Americans of all ages, including approximately 300,000 American children under the age of 14.

"FDA-approved therapies for children with epilepsy are limited, so any medication that can be clinically proven to effectively control seizures in this population with a favorable tolerability profile, provides an important new option to manage this condition," said Michael Duchowny, M.D., director of the Comprehensive Epilepsy Program at Miami Children's Hospital. "Lamictal is a welcome addition for children whose partial seizures are inadequately controlled on their existing therapy."

Approval of Lamictal was based on a clinical study, published in the journal Neurology, demonstrating the efficacy of the drug as add-on therapy in pediatric patients who were still having frequent partial seizures (at least four per month) despite optimal doses of other antiepilepsy drugs (AEDs).

According to Dr. Duchowny, a lead investigator in this study, there were significant reductions in the frequency of all partial seizures in children and adolescents with epilepsy when Lamictal was added to their AED regimen. In the 18-week, double-blind, placebo-controlled study, 199 patients, ages two to 16 years who were still having frequent seizures despite use of other AEDs, were randomized to treatment with Lamictal or placebo added to their current AED regimen of up to two drugs (Lamictal: 98, placebo: 101). The primary efficacy endpoint was percentage change from baseline in all partial seizures. The key study results, all of which are statistically significant, are:

  • Patients treated with Lamictal as adjunctive therapy experienced a 36% reduction in frequency of all partial seizures, vs. 7% in placebo group
  • Forty-two percent (42%) of Lamictal patients experienced a 50% reduction in partial seizures, vs. 16% in placebo group
  • Patients receiving Lamictal experienced more days without seizures (a median increase of 28% in days free of all partial seizures) than those in the placebo group (3.2%)

"The results of this study continue to reinforce our overall understanding of the potential for use of Lamictal for a number of seizure types, including children, who often have unique needs," said John Messenheimer, M.D., director of the epilepsy clinical research group at GlaxoSmithKline. "This approval clearly expands the potential for this important therapeutic agent."

Adverse events in the study that occurred at a significantly higher frequency in patients treated with Lamictal compared with patients treated with placebo were dizziness (21% in patients taking Lamictal vs. 5% in patients taking placebo), ataxia (10% vs. 2%), tremor (12% vs. 2%), and nausea (11% vs. 2%). However, most adverse events were rated as mild or moderate in severity. Adverse events led to withdrawal of six patients treated with placebo and five patients treated with Lamictal. Two patients treated with Lamictal were hospitalized due to serious rash, which resolved in both patients after discontinuation of Lamictal.

It should be noted that the initial dose and dose escalation of Lamictal in this study was higher than is currently recommended for pediatric patients.

SAFETY INFORMATION ON LAMICTAL
Lamictal is indicated as adjunctive therapy for partial seizures in adults and pediatric patients (³ two years of age) and as adjunctive therapy for the generalized seizures of Lennox-Gastaut syndrome in adult and pediatric patients (³ two years of age). Lamictal is indicated for conversion to monotherapy in adults with partial seizures who are receiving treatment with a single enzyme-inducing AED.

Safety and effectiveness of Lamictal have not been established as initial monotherapy, for conversion to monotherapy from non-enzyme?inducing AEDs (e.g., valproate), or for simultaneous conversion to monotherapy from two or more concomitant AEDs. See Dosage and Administration section in Prescribing Information. Safety and effectiveness in patients below the age of 16 other than those with partial seizures and the generalized seizures of Lennox?Gastaut syndrome have not been established.

Serious rashes requiring hospitalization and discontinuation of treatment have been reported in association with the use of Lamictal. The incidence of these rashes, which have included Stevens?Johnson Syndrome, is approximately 0.8% (8 per 1,000) in pediatric patients under the age of 16 years receiving Lamictal as adjunctive therapy, and 0.3% (3 per 1,000) in adults. In a prospectively followed cohort of 1,983 pediatric patients taking adjunctive Lamictal, there was one rash-related death. In worldwide post-marketing experience, rare cases of toxic epidermal necrolysis (TEN) and/or rash?related death have been reported in adult and pediatric patients, but their numbers are too few to permit a precise estimate of the rate.

Because the rate of serious rash is greater in pediatric patients than in adults, it bears emphasis that Lamictal is approved only for use in pediatric patients below the age of 16 years who have partial seizures or seizures associated with the Lennox?Gastaut syndrome (see Indications Section in Prescribing Information).

Other than age, there are as yet no factors identified that are known to predict the risk of occurrence or the severity of rash associated with Lamictal. There are suggestions, yet to be proven, that the risk of rash may also be increased by co-administration of Lamictal with valproic acid, exceeding the recommended initial dose of Lamictal, or exceeding the recommended dose escalation for Lamictal. However, cases have been reported in the absence of these factors.

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GlaxoSmithKline, with U.S. operations in Philadelphia and Research Triangle Park, N.C., is one of the world's leading research-based pharmaceutical and health care companies. GlaxoSmithKline is committed to improving the quality of human life by enabling people to do more, feel better and live longer. More information on GlaxoSmithKline is available at the company's web site at www.gsk.com.

Editors' Note: For Full Prescribing Information, please call Kristi Reeves at (919) 483-2839.

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