Research Triangle Park, NC, August 29, 2002 - GlaxoSmithKline (GSK) announced today it is seeking the first-ever indication for long-term management of bipolar I disorder to delay the relapse/recurrence of depressive episodes. GSK filed a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for Lamictal® (lamotrigine).

An estimated 2.3 million American adults have bipolar disorderⁱ (also known as manic-depression). The depressive phase of bipolar disorder, often referred to as bipolar depression, is a serious condition that puts people at significant risk for suicide and other harmful behaviors. In fact, approximately 1 in 5 people with bipolar disorder attempt suicide, typically during a depressed or mixed (depression and mania) episode.ⁱⁱ

"Many effective treatments are available for the acute mania associated with bipolar disorder, but with no approved long-term treatments to delay bipolar depression, there is a critical unmet need for people facing the devastating lows of this illness," said Robert Leadbetter, M.D., director of Psychiatry Clinical Development and Medical Affairs at GlaxoSmithKline. "This filing signals our confidence in Lamictal as a potential treatment option for the millions of people with bipolar I disorder."

The application for approval of Lamictal as long-term management of adult patients with bipolar I disorder to delay the relapse/recurrence of depressive episodes is supported by two landmark 18-month studies, some of the largest and longest ever conducted in bipolar disorder. Results of the two double-blind, placebo-controlled studies of 638 adult patients demonstrated Lamictal significantly delayed the relapse/recurrence of mood episodes, particularly depressive episodes, in patients with bipolar I disorder.

"In these trials, Lamictal significantly delayed the time to any bipolar episode and, most strikingly, the depression associated with bipolar disorder," said lead study investigator, Joseph R. Calabrese, M.D., director of the Mood Disorders Center at the University Hospitals of Cleveland and professor of psychiatry at the Case Western University School of Medicine. "These findings are particularly important because bipolar disorder is a chronic illness that requires long-term management."

In these long-term studies of Lamictal, the most common adverse events were back pain, fatigue, abdominal pain, nausea, constipation, vomiting, insomnia, somnolence, xerostomia (dry mouth), rhinitis, exacerbation of cough, pharyngitis and rash. Further, the common adverse events reported with Lamictal treatment during the dose escalation phase of the bipolar I disorder studies included headache, rash, dizziness, diarrhea, dream abnormality, pruritis and tremor.

About Bipolar Disorder
Bipolar disorder is a chronic, sometimes progressive illness characterized by distressing and disruptive mood swings from high to low states. If manic and depressive symptoms overlap for a period of time, it is called a "mixed" episode.ⁱⁱⁱ Bipolar I disorder is characterized by the occurrence of one or more manic or mixed episodes and often individuals have also had one or more major depressive episodes; in bipolar II disorder, a person experiences hypomania (a milder form of mania with less severe symptoms) and depression. Although there is no cure for bipolar disorder, the updated American Psychiatric Association (APA) guidelines stress that treatment can significantly decrease the associated symptoms and mortality rate.^iv Bipolar disorder may be associated with suicide in nearly 10-15 percent of patients,^v making it one of the most serious and deadly psychiatric illnesses. When not adequately treated, bipolar disorder can worsen and patients can experience a greater frequency of events.^vii

Additionally, researchers estimate that more than 40 percent of individuals with bipolar disorder abuse alcohol or drugs during their illness.^viii Misdiagnosis and delayed treatment of bipolar disorder are common, with patients going an average of 8 years without an accurate diagnosis.^ix

About Lamictal
Lamictal is available in over 90 countries and has been available in the U.S. since 1994. It has been used by over 3 million patients worldwide.

Lamictal is currently indicated as adjunctive therapy in adults with partial seizures and as adjunctive therapy in the generalized seizures of Lennox-Gastaut syndrome in pediatric and adult patients.

Lamictal is indicated for conversion to monotherapy in adults with partial seizures who are receiving treatment with an enzyme-inducing antiepileptic drug.

The safety and effectiveness of Lamictal have not been established as initial monotherapy in the treatment of epilepsy; for conversion to monotherapy from non-enzyme-inducing AEDs (e.g., valproate); or for simultaneous conversion to monotherapy from two or more concomitant AEDs. Safety and effectiveness in patients below the age of 16 other than those with 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 one percent (1/100) in pediatric patients less than 16 years old and 0.3 percent (3/1,000) in adults. In worldwide post-marketing experience, rare cases of toxic epidermal necrolysis (TEN) and/or rash-related death have been reported, but their numbers are too few to permit a precise estimate of the rate. Lamictal ordinarily should be discontinued at the first signs of rash, unless the rash is clearly not drug-related.

The risk of nonserious rash is increased when the recommended initial dose and/or the rate of dose escalation of Lamictal is exceeded. There are suggestions, yet to be proven, that the risk of severe, potentially life- threatening rash may be increased by 1) coadministration of Lamictal with valproic acid; 2) exceeding the recommended initial dose of Lamictal; or 3) exceeding the recommended dose escalation of Lamictal. However, cases have been reported in the absence of these factors. Therefore, it is important that the dosing recommendations be followed closely.

GlaxoSmithKline, one of the world's leading research-based pharmaceutical and healthcare companies, is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

Updated August 29, 2002 - © 2001-2005 GlaxoSmithKline - All Rights Reserved Legal Notices - Privacy Statement - Accessibility