WILMINGTON, Del., Feb. 29 /PRNewswire-FirstCall/ -- AstraZeneca (NYSE:
AZN) today announced the submission of a supplemental New Drug Application
(sNDA) to the U.S. Food and Drug Administration (FDA) for once- daily
SEROQUEL XR(TM) (quetiapine fumarate) Extended-Release Tablets to seek
approval for the treatment of major depressive disorder (MDD) as
monotherapy, adjunct therapy, and maintenance therapy in adult patients.
MDD affects 15 million American adults -- between 5 and 8 percent of
the population each year -- and today it is often treated with generic or
branded antidepressants.(1) Studies have shown that at least one-third of
patients with MDD treated with antidepressants fail to achieve a
satisfactory response.(2) The American Psychiatric Association Practice
Guidelines recommend switching to a medication in another class when two
medications from the same class have proven ineffective.(3) AstraZeneca has
investigated the use of SEROQUEL XR, an atypical antipsychotic, in the
treatment of MDD, aiming to develop another potential treatment option,
including treatment for patients who have failed or had an inadequate
response to another antidepressant therapy.
The MDD submission is based on seven Phase III, placebo-controlled
studies that assessed the efficacy and safety of once-daily treatment with
SEROQUEL XR in patients diagnosed with MDD. Studies 1, 2, 3, and 4 were
acute monotherapy studies involving 2,116 patients; Studies 6 and 7 were
acute adjunct therapy studies (with ongoing antidepressant therapy)
involving 939 patients who had an inadequate response to an antidepressant
therapy; and Study 5 was a longer-term (up to 78 weeks) monotherapy
maintenance study involving 1,854 patients. The acute studies included in
this submission used the Montgomery-Asberg Depression Rating Scale (MADRS)*
as the primary assessment of depression symptoms. In the longer-term study
(Study 5), the primary assessment was time to a depressed event using
criteria including the MADRS. Doses of 50 mg, 150 mg and 300 mg of SEROQUEL
XR were studied in the MDD program.(4)
In 2007, SEROQUEL XR was approved in the U.S. for the treatment of
schizophrenia in adult patients and for maintenance treatment of
schizophrenia in adult patients. Last month, AstraZeneca announced the
submission of two separate sNDAs to the FDA for SEROQUEL XR to seek
approval for the treatment of manic episodes associated with bipolar
disorder and the treatment of depressive episodes associated with bipolar
disorder. The FDA has not completed its review of these submissions. In
addition to the submission for MDD, clinical development programs are
ongoing and regulatory filings are planned for SEROQUEL XR in other
indications.
Launched in 1997, SEROQUEL(R) (quetiapine fumarate tablets) has been
prescribed to millions of patients worldwide. It is approved in 88
countries for the treatment of schizophrenia, in 79 countries for the
treatment of bipolar mania, and in 11 countries including the U.S. for the
treatment of bipolar depression.
Important Safety Information for SEROQUEL and SEROQUEL XR
SEROQUEL XR is indicated for the acute and maintenance treatment of
schizophrenia. SEROQUEL is indicated for the treatment of depressive
episodes in bipolar disorder; acute manic episodes in bipolar I disorder,
as either monotherapy or adjunct therapy to lithium or divalproex; and
schizophrenia. Patients should be periodically reassessed to determine the
need for treatment beyond the acute response.
Elderly patients with dementia-related psychosis treated with atypical
antipsychotic drugs are at an increased risk (1.6 to 1.7 times) of death,
compared to placebo (4.5% vs 2.6%, respectively). SEROQUEL and SEROQUEL XR
are not approved for the treatment of patients with dementia-related
psychosis. (See Boxed Warning.)
Antidepressants increased the risk of suicidal thinking and behavior in
children, adolescents, and young adults in short-term studies of major
depressive disorder and other psychiatric disorders. Patients of all ages
started on therapy should be observed closely for clinical worsening,
suicidality, or unusual changes in behavior. Families and caregivers should
be advised of the need for close observation and communication with the
prescriber. SEROQUEL and SEROQUEL XR are not approved for use in patients
under the age of 18 years. SEROQUEL XR is not approved for the treatment of
depression; however, SEROQUEL is approved for the treatment of bipolar
depression. (See Boxed Warning.)
Hyperglycemia, in some cases extreme and associated with ketoacidosis,
hyperosmolar coma, or death, has been reported in patients treated with
atypical antipsychotics, including quetiapine. The relationship of atypical
use and glucose abnormalities is complicated by the possibility of
increased risk of diabetes in the schizophrenic population and the
increasing incidence of diabetes in the general population. However,
epidemiological studies suggest an increased risk of treatment-emergent,
hyperglycemia-related adverse events in patients treated with atypical
antipsychotics. Patients starting treatment with atypical antipsychotics
who have or are at risk for diabetes should undergo fasting blood glucose
testing at the beginning of and periodically during treatment. Patients who
develop symptoms of hyperglycemia should also undergo fasting blood glucose
testing.
A potentially fatal symptom complex, sometimes referred to as
Neuroleptic Malignant Syndrome (NMS), has been reported in association with
administration of antipsychotic drugs, including quetiapine. Rare cases of
NMS have been reported with quetiapine. Clinical manifestations of NMS are
hyperpyrexia, muscle rigidity, altered mental status, and evidence of
autonomic instability (irregular pulse or blood pressure, tachycardia,
diaphoresis, and cardiac dysrhythmia). Additional signs may include
elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute
renal failure. The management of NMS should include immediate
discontinuation of antipsychotic drugs.
Tardive dyskinesia (TD), a potentially irreversible syndrome of
involuntary dyskinetic movements, may develop in patients treated with
antipsychotic drugs. The risk of developing TD and the likelihood that it
will become irreversible are believed to increase as the duration of
treatment and total cumulative dose of antipsychotic drugs administered to
the patient increase. TD may remit, partially or completely, if
antipsychotic treatment is withdrawn. Quetiapine should be prescribed in a
manner that is most likely to minimize the occurrence of TD.
Leukopenia, neutropenia, and agranulocytosis (including fatal cases),
have been reported temporally related to atypical antipsychotics, including
quetiapine. Patients with a pre-existing low white blood cell (WBC) count
or a history of drug induced leukopenia/neutropenia should have their
complete blood count monitored frequently during the first few months of
therapy. In these patients, SEROQUEL and SEROQUEL XR should be discontinued
at the first sign of a decline in WBC absent other causative factors.
Patients with neutropenia should be carefully monitored, and SEROQUEL and
SEROQUEL XR should be discontinued in any patient if the absolute
neutrophil count is < 1000/mm.
Warnings and Precautions also include the risk of orthostatic
hypotension, cataracts, seizures and hyperlipidemia. Examination of the
lens by methods adequate to detect cataract formation, such as slit lamp
exam or other appropriately sensitive methods, is recommended at initiation
of treatment, or shortly thereafter, and at 6-month intervals during
chronic treatment.
The most commonly observed adverse events associated with the use of
SEROQUEL monotherapy versus placebo in clinical trials for schizophrenia
and bipolar disorder were dry mouth (9%-44% vs 3%-13%), sedation (30% vs
8%), somnolence (18%-28% vs 7%-8%), dizziness (11%-18% vs 5%-7%),
constipation (8%-10% vs 3%-4%), SGPT increase (5% vs 1%), dyspepsia (5%-7%
vs 1%-4%), lethargy (5% vs 2%), and weight gain (5% vs 1%). The most
commonly observed adverse events associated with the use of SEROQUEL versus
placebo in clinical trials as adjunct therapy with lithium or divalproex in
bipolar mania were somnolence (34% vs 9%), dry mouth (19% vs 3%), asthenia
(10% vs 4%), constipation (10% vs 5%), abdominal pain (7% vs 3%), postural
hypotension (7% vs 2%), pharyngitis (6% vs 3%), and weight gain (6% vs 3%).
The most commonly observed adverse events associated with the use of
SEROQUEL XR versus placebo in clinical trials for schizophrenia were dry
mouth (12% vs 1%), constipation (6% vs 5%), dyspepsia (5% vs 2%), sedation
(13% vs 7%), somnolence (12% vs 4%), dizziness (10% vs 4%), and orthostatic
hypotension (7% vs 5%).
In long-term clinical trials of quetiapine, hyperglycemia (fasting
glucose 126 mg/dL) was observed in 10.7% of patients receiving quetiapine
(mean exposure 213 days) vs 4.6% in patients receiving placebo (mean
exposure 152 days).
Please see Prescribing Information, including Boxed Warnings, for
SEROQUEL (http://www1.astrazeneca-us.com/pi/seroquel.pdf) and SEROQUEL XR
(http://www1.astrazeneca-us.com/pi/seroquelxr.pdf).
About Major Depressive Disorder
Major depressive disorder is a serious medical illness affecting 15
million American adults, or approximately 5 to 8 percent of the adult
population in a given year. Depression occurs twice as frequently in women
as in men. Unlike normal emotional experiences of sadness, loss, or passing
mood states, major depressive disorder is persistent and can significantly
interfere with an individual's thoughts, behavior, mood, activity, and
physical health. Among all medical illnesses, major depressive disorder is
the leading cause of disability in the U.S. and many other developed
countries.(1)
Symptoms of major depressive disorder characteristically represent a
significant change from how a person functioned before the illness. The
symptoms of depression include: persistently sad or irritable mood;
pronounced changes in sleep, appetite, and energy; difficulty thinking,
concentrating, and remembering; physical slowing or agitation; lack of
interest in or pleasure from activities that were once enjoyed; feelings of
guilt, worthlessness, hopelessness, and emptiness; recurrent thoughts of
death or suicide; and persistent physical symptoms for two or more weeks
that do not respond to treatment, such as headaches, digestive disorders,
and chronic pain.(1) Symptomatically, a major depressive episode in MDD is
similar to a depressive episode of bipolar disorder with the major
distinguishing feature between the disorders being the absence of manic or
hypomanic symptoms in MDD.(6) It has been reported that 69 percent of
patients with bipolar disorder were misdiagnosed, with the most frequent
misdiagnosis being MDD.(7)
Without treatment, the frequency of depressive illness as well as the
severity of symptoms tends to increase over time. Left untreated,
depression can lead to suicide.(1)
About AstraZeneca
AstraZeneca is a major international healthcare business engaged in the
research, development, manufacturing and marketing of meaningful
prescription medicines and supplier for healthcare services. AstraZeneca is
one of the world's leading pharmaceutical companies with healthcare sales
of $29.55 billion and is a leader in gastrointestinal, cardiovascular,
neuroscience, respiratory, oncology and infectious disease medicines. In
the United States, AstraZeneca is a $13.35 billion dollar healthcare
business with 12,200 employees committed to improving people's lives.
AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as
well as the FTSE4Good Index.
For more information visit http://www.astrazeneca-us.com.
The statements contain herein include forward-looking statements.
Although we believe our expectations are based on reasonable assumptions,
any forward-looking statements, by their very nature, involve risks and
uncertainties and may be influenced by factors that could cause actual
outcomes and results to be materially different from those predicted. The
forward-looking statements reflect knowledge and information available at
the date of the preparation of this press release and the Company
undertakes no obligation to update these forward-looking statements.
Important factors that could cause actual results to differ materially from
those contained in forward-looking statements, certain of which are beyond
our control, include, among other things, those risk factors identified in
the Company's Annual Report/Form 20-F for 2006. Nothing contained herein
should be construed as a profit forecast.
* The Montgomery-Asberg Depression Rating Scale (MADRS) measures the
severity of a number of depressive symptoms including sadness, tension,
sleep, appetite, energy, concentration, and suicidal ideation. The MADRS
score decreases as depressive symptoms improve.(5)
References
1. National Alliance on Mental Illness: Major Depression Fact Sheet. 2007. Available at:
http://www.nami.org/Template.cfm?Section=By_Illness&Template=/TaggedPage/Ta
gge dPageDisplay.cfm&TPLID=54&ContentID=26414 (Due to length of URL, please
cut
and paste into browser). Accessed November 30, 2007.
2. Nemeroff, CB. Prevalence and Management of Treatment-Resistant
Depression. J Clin Psychiatry. 2007;68:17-25.
3. American Psychiatric Association. Practice Guideline for the Treatment
of Patients With Major Depressive Disorder, Second Edition. April 2002.
http://www.psychiatryonline.com/content.aspx?aID=48727
4. Data on file, DA-SXR-12 5. Lundbeck Institute. Psychiatric Rating Scales. PDF available at:
http://www.brainexplorer.org/factsheets/Psychiatry%20Rating%20Scales.pdf
(Due
to length of URL, please cut and paste into browser). Accessed on
May 5, 2006.
6. American Psychiatric Association. Diagnostic and Statistical Manual of
Mental Disorders. Fourth Edition Text Revision. Washington DC: 2000.
7. Hirschfeld RM, Lewis L, Vornik LA. Perceptions and Impact of Bipolar
Disorder: How Far Have We Really Come? Results of the National
Depressive and Manic-Depressive Association 2000 Survey of Individuals
with Bipolar Disorder. J Clin Psychiatry. 2003;64:161-174.
SOURCE AstraZeneca
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Related links:
http://www.astrazeneca-us.com
http://www1.astrazeneca-us.com/pi/seroquel.pdf
http://www1.astrazeneca-us.com/pi/seroquelxr.pdf
http://www.prnewswire.com/comp/985887.html/
CONTACT:
Jim Minnick, +1-302-886-5135,
jim.minnick@astrazeneca.com, or Abigail Baron, +1-302-885-3578,
abigail.baron@astrazeneca.com, both of AstraZeneca
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