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Research Triangle Park, NC, June 23, 2003 -
GlaxoSmithKline (NYSE: GSK) announced today the U.S. Food
and Drug Administration’s (FDA) approval of
Lamictal® (lamotrigine) tablets for the long-term
maintenance treatment of Bipolar I Disorder. Specifically, the FDA
approved Lamictal for the maintenance treatment of adults with
Bipolar I Disorder to delay the time to occurrence of mood episodes
(depression, mania, hypomania, mixed episodes) in patients treated
for acute mood episodes with standard therapy. Additionally, the FDA
has noted that findings for Lamictal maintenance treatment
were more robust in bipolar depression. Maintenance treatment of
bipolar depression is one of the most significant medical needs in
the treatment of this devastating illness. The effectiveness of
Lamictal in the acute treatment of mood episodes has not been
established. Lamictal is the first FDA-approved therapy since
Lithium for maintenance treatment of bipolar I disorder.
Bipolar disorder, a serious, chronic illness marked by disabling
mood swings from high (manic) to low (depressed) states,1
is one of the most common mental illnesses in the United States.
Recent research suggests bipolar symptoms may affect three times as
many people -- nearly eight million American adults (or one in 30
people) -- as previously believed.2 A recent study in
patients with bipolar disorder showed that the total time spent
depressed exceeded time spent manic by a factor of three, indicating
that the depressive phases of bipolar illness were more problematic
and treatment-resistant.3 Most attempted and completed
suicides occur during the depressive or mixed phases.
"The finding that Lamictal possesses long-term efficacy in the
treatment of bipolar disorder is extremely important," said Joseph
R. Calabrese, M.D., Director of the Mood Disorders Center,
University Hospitals of Cleveland and professor of psychiatry, Case
Western University School of Medicine. "The last time the FDA
approved a long-term treatment for bipolar disorder was lithium in
the 1970s. In addition, the results are more robust for depression,
the phase of illness in which patients spend the majority of their
time."
The FDA’s approval of Lamictal was based on the results of
two landmark, randomized, placebo-controlled 18-month studies, which
evaluated adult patients who were either currently or recently manic
or depressed. Combined, these studies represent the largest,
prospectively defined, placebo-controlled maintenance data set in
bipolar disorder (1,305 patients). Following the open-label phase,
patients who reached stabilization criteria entered the randomized
phase. Findings from these studies show Lamictal
significantly delays the time to intervention for mood episodes
(depression, mania, hypomania, and mixed episodes) in patients with
bipolar I disorder. Intervention was defined as additional
pharmacotherapy or electroconvulsive therapy (ECT) for a mood
episode or one that was emerging. Specifically, in recently
depressed patients, the median days to intervention were 200 for
Lamictal and 93 for placebo, which represents 115% more
intervention-free days. Similarly, in recently manic or hypomanic
patients, the median days to intervention was 141 for Lamictal and
85 for placebo, which represents 66 percent more intervention-free
days. The combined analysis for the two studies revealed a
statistically significant benefit for Lamictal over placebo in
delaying the time to occurrence of both depression and mania,
although the finding was more robust for depression. Lamictal
was associated with a favorable tolerability profile in these
studies.
The most common (=5% and numerically >placebo) side effects
associated with Lamictal in the randomized phase of these studies
were: nausea (14%) insomnia (10%) somnolence (9%) back pain (8%)
fatigue (8%) rhinitis (7%) non-serious rash, (7%), abdominal pain
(6%) dry mouth (6%), constipation (5%), vomiting (5%), exacerbation
of cough (5%) pharyngitis (5%). Adverse events that occurred in =5%
and were numerically more common in patients during the dose
escalation phase of these trials, when patients may have been
receiving concomitant psychotropic medications, compared to the
monotherapy phase were: headache (25%), rash (11%), dizziness (10%),
diarrhea (8%), dream abnormality (6%) and pruritus (6%).
Serious rashes requiring hospitalization and discontinuation of
treatment have been reported in association with the use of
Lamictal. For further important safety information on serious rash,
see "About Lamictal" section below and accompanying prescribing
information.
"Combined, these studies are unique in that they not
only included bipolar patients who were recently manic but also
others who were recently depressed, which is reflective of how
bipolar patients present in the clinic," said Robert Leadbetter,
M.D., Senior Director of Psychiatry, clinical Development and
Medical Affairs at GlaxoSmithKline. "Going into these studies, our
goal was to extend stability by delaying the time to occurrence of
mood episodes and we are excited by the results achieved by patients
on Lamictal, compared to those on placebo."
About Bipolar Disorder
Bipolar I disorder is characterized by the occurrence of one or
more manic or mixed episodes and often individuals also have had one
or more major depressive episodes; in bipolar II disorder, a person
experiences one or more major depressive episodes and hypomania (a
milder form of mania with less severe symptoms). If manic and
depressive symptoms overlap for a period of time, it is called a
"mixed" episode.
Although there is no cure for bipolar disorder, the revised APA
treatment guidelines stressed that treatment can significantly
improve symptoms associated with the illness.4 One of the
most serious risks of bipolar disorder is suicide, which is
associated most often with the depressive
phase.5
Suicide completion rates may be as high as 10-15 percent of
patients with bipolar I disorder6 making it one of the
most serious and deadly psychiatric illnesses. Additionally,
researchers estimate that more than 40 percent of individuals with
bipolar disorder have problems with alcohol or drugs during their
illness.7 When left untreated, bipolar disorder
can worsen and patients can experience a greater frequency of
events. For more information on bipolar I disorder, visit
www.bipolar.com.
About Lamictal
Lamictal is available in over 90 countries and has been used by
an estimated 5 million patients worldwide.
Lamictal has been available in the U.S. since 1994 and also is
indicated as adjunctive therapy for partial seizures in adults and
pediatric patients (³ 2 years of age).
Lamictal is also indicated as adjunctive therapy for the generalized
seizures of Lennox-Gastaut syndrome in adult and pediatric patients
(³ 2 years of age). Lamictal is indicated
for conversion to monotherapy in adults with partial seizures who
are receiving treatment with a single enzyme-inducing antiepileptic
drug.
The safety and effectiveness of Lamictal have not been
established 1) as initial monotherapy, 2) for conversion to
monotherapy from non-enzyme-inducing anti epileptic drugs (e.g.
valproate), or 3) for simultaneous conversion to monotherapy from 2
or more concomitant AEDs). 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 percent (8/1,000) in
pediatric patients under the age of 16 years receiving Lamictal as
adjunctive therapy for epilepsy, and 0.3 percent (3/1,000) in adults
on adjunctive therapy for epilepsy. In clinical trials of bipolar
and other mood disorders, the rate of serious rash was 0.08 percent
(0.8/1,000) in adult patients receiving Lamictal as initial
monotherapy and 0.13 percent (1.3/1,000) in adult patients receiving
Lamictal as adjunctive therapy.
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, 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. For more
information on Lamictal, log on to www.lamictal.com.
GlaxoSmithKline, one of the world's leading research-based
pharmaceutical and health care companies, is committed
to improving the quality of human life by enabling people to do
more, feel better and live longer.
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Ramona DuBose |
GlaxoSmithKline |
(919) 483-2839 |
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