WILMINGTON, Del., May 8 /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 SEROQUEL XR(TM)
(quetiapine fumarate) Extended-Release Tablets to seek approval for the
treatment of generalized anxiety disorder (GAD), including maintenance of
antianxiety effect. It is the first time approval has been sought for an
atypical antipsychotic medicine in GAD. The submission is based on a robust
clinical development program involving more than three thousand patients.
This week, at the 161st Annual Meeting of the American Psychiatric
Association (APA) in Washington, D.C., data from two of the studies
(Studies 9 and 12) supporting the submission were presented.
GAD, which affects approximately 6.8 million adults in the U.S., is
characterized by persistent anxiety, exaggerated worry and tension. GAD is
diagnosed when someone excessively worries about a number of everyday
problems for at least 6 months.(1,2) Several classes of drugs have
demonstrated efficacy in the treatment of GAD. Treatment typically includes
selective- serotonin reuptake inhibitors (SSRIs) or serotonin
norepinephrine reuptake inhibitors (SNRIs); however, approximately 30
percent of patients do not achieve an adequate response to short-term
treatment.(3) Benzodiazepines, commonly prescribed antianxiety medications,
may be used for the rapid relief of anxiety symptoms, but long-term use of
these agents is not generally recommended.(4)
The GAD submission is based on four Phase III efficacy and safety
studies. Three short-term, multicenter, double-blind, randomized,
placebo-controlled studies (Studies 9, 10, and 11) compared the safety and
efficacy of SEROQUEL XR at doses of 50 mg, 150 mg and 300 mg to placebo for
eight weeks in outpatients with GAD. Active controls were also used in
Study 10 (escitalopram 10 mg daily) and Study 11 (paroxetine 20 mg daily).
These short-term studies used the Hamilton Rating Scale for Anxiety
(HAM-A)* as the primary assessment of anxiety symptoms.(5-8)
Study 12 was a long-term, multicenter, randomized-withdrawal, parallel-
group, placebo-controlled, Phase III study that comprised four phases: an
enrollment period of up to 28 days, an open-label run-in treatment period
of four to eight weeks, an open-label stabilization treatment period of 12
to 18 weeks, and a randomized-withdrawal treatment period of up to 52
weeks. The SEROQUEL XR dose was flexible: 50 mg, 150 mg, or 300 mg once
daily, based on the clinical judgment of the investigator. In this
longer-term study, the primary assessment was time from randomization to an
anxiety event.(8)
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. SEROQUEL XR is currently not approved for
the treatment of bipolar disorder. In January 2008, 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. In February 2008, AstraZeneca filed a sNDA for SEROQUEL XR to
seek approval for the treatment of MDD as monotherapy, adjunct therapy, and
maintenance therapy. The FDA has not completed its review of these
submissions.
IMPORTANT SAFETY INFORMATION FOR SEROQUEL XR
SEROQUEL XR is indicated for the acute and maintenance treatment of
schizophrenia. Patients should be periodically reassessed to determine the
need for maintenance treatment and the appropriate dose.
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 XR is 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 XR is not approved for use in patients under the age
of 18 years. SEROQUEL XR is not approved for the treatment of depression;
however, an immediate release form of quetiapine 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 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 XR should be
discontinued in any patient if the absolute neutrophil count is less than
1000 per cubic millimeter.
Warnings and Precautions also include the risk of orthostatic
hypotension, cataracts, seizures, hyperlipidemia, and possibility of
suicide attempts. 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 possibility of a
suicide attempt is inherent in schizophrenia, and close supervision of high
risk patients should accompany drug therapy.
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 greater than or equal to 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 XR.
About Generalized Anxiety Disorder (GAD)
GAD is characterized by chronic anxiety, exaggerated worry, and
tension, even when there is little or nothing to provoke it.(1,2) People
with GAD anticipate disaster and are overly concerned about health issues,
money, family problems, or difficulties at work.
People with GAD can't seem to get rid of their concerns, even though
they usually realize that their anxiety is more intense than the situation
warrants.(1,2) They can't relax, startle easily, and have difficulty
concentrating. Often they have trouble falling asleep or staying asleep.
Physical symptoms that often accompany the anxiety include fatigue,
headaches, muscle tension, muscle aches, difficulty swallowing, trembling,
twitching, irritability, sweating, nausea, lightheadedness, having to go to
the bathroom frequently, feeling out of breath, and hot flashes. GAD is
diagnosed when someone excessively worries about a number of everyday
problems for at least 6 months.
In the U.S. GAD affects about 6.8 million adults, with women twice as
likely to develop GAD as men.(1,2) The disorder comes on gradually and can
begin across the life cycle. GAD rarely occurs alone and is often
accompanied by other anxiety disorders, depression, or substance abuse.
Genetic factors are also thought to be involved.
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 2007. Nothing contained herein
should be construed as a profit forecast.
* The HAM-A rating scale consists of 14 items and measures the severity
of symptoms such as anxiety, tension, depressed mood, palpitations,
breathing difficulties, sleep disturbances, restlessness, and other
physical symptoms.(9)
References
1. National Institute of Mental Health: Anxiety Disorders. NIH
Publication No. 06-3879. Available at: (Due to URL length, please copy and paste into browser)
http://www.nimh.nih.gov/health/publications/anxiety-disorders/generalized-
anxiety-disorder-gad.shtml
Accessed March 20, 2008.
2. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,
Text Revision. Washington, DC: American Psychiatric Association;
2000:472-475.
3. Rickels K and Ryann M. Pharmacotherapy of Generalized Anxiety
Disorder. J Clin Psychiatry. 2002;63 (suppl 14): 9-16.
4. Schmitt R, Gazalle FK, Silva de Lima M, et al. The efficacy of
antidepressants for generalized anxiety disorder: a systematic review
and meta-analysis. The Brazilian Journal of Psychiatry. 2005;
27(1):18-24.
5. Data on File, DA-SXR-15, AstraZeneca LP.
6. Joyce M, Khan A, Atkinson S, et al. Efficacy and safety of extended
release Quetiapine fumarate (quetiapine XR) monotherapy in patients
with generalized anxiety disorder (GAD) [poster]. Presented at: The
Annual Meeting of the American Psychiatric Association; May 3-8, 2008,
Washington, D.C., USA.
7. Chouinard G, Bandelow B, Ahokas A, et al. Once-daily extended release
of quetiapine fumarate (quetiapine XR) monotherapy in generalized
anxiety disorder: a Phases III, double-blind, placebo-controlled study
[poster]. Presented at: The Annual Meeting of The American College of
Neuropsychopharmacology; December 9-13, 2007, Boca Raton, FL.
8. Katzman M, Brawman-Mintzer O, Reyes E, et al. Extended Release
quetiapine fumarate (quetiapine XR) monotherapy in maintenance
treatment of generalized anxiety disorder (GAD): efficacy and
tolerability results from a randomized, placebo-controlled trial
[poster]. Presented at: The Annual Meeting of the American Psychiatric
Association; May 3-8, 2008, Washington, D.C., USA.
9. Lundbeck Institute. Psychiatric Rating Scales. PDF available at:
http://www.brainexplorer.org/factsheets/Psychiatry%20Rating%20Scales.pdf.
Accessed on May 2, 2008.
SOURCE AstraZeneca
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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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