WILMINGTON, Del., Dec. 30 /PRNewswire-FirstCall/ -- AstraZeneca today announced that it has submitted a supplemental New Drug Application (sNDA) with the US Food and Drug Administration (FDA) to seek approval for a new indication for SEROQUEL(R) (quetiapine fumarate) for the treatment of patients with depressive episodes associated with bipolar disorder. SEROQUEL is currently approved for the treatment of acute manic episodes associated with bipolar I disorder and the treatment of schizophrenia.
“AstraZeneca is dedicated to improving patients’ lives and developing new treatments for mental illness,” said Wayne Macfadden, MD, US Medical Director for SEROQUEL. “This sNDA submission is an important milestone in the history of SEROQUEL. If SEROQUEL receives approval from the FDA to treat bipolar depression, it would be the only single agent indicated to treat both the depressive and manic episodes associated with bipolar disorder.”
The sNDA submission is based on results from the clinical trial program known as BOLDER (BipOLar DEpRession), which comprises two studies: BOLDER I and BOLDER II. Both studies were double-blind, placebo-controlled trials of outpatients (N=1,045) with bipolar I or II disorder. Patients were randomized to receive eight weeks of treatment with fixed doses of SEROQUEL (300 mg or 600 mg) or placebo administered once daily. In both studies, patients receiving SEROQUEL, as compared to those receiving placebo, showed a statistically significant decrease in depression scores* at week one, and scores continued to decrease throughout the eight-week study. More than half of the SEROQUEL treated patients in each trial met the criteria for remission.(1)
Additionally, SEROQUEL was shown to have similar safety profiles in both BOLDER I and II. The most common adverse effects reported in these trials included dry mouth, sedation, somnolence, dizziness, and constipation.(1)
Bipolar disorder, which affects more than 7 million American adults(2), consists of recurring episodes of mania and depression. Patients with bipolar disorder are symptomatic almost half of their lives, and approximately two- thirds of that time is spent in the depressed phase of the illness(3). Prolonged periods of sadness, unexplained loss of energy, persistent lethargy, and recurring thoughts of death or suicide characterize depressive episodes(4). Up to 50 percent of patients with bipolar depression attempt suicide, and approximately 10 to 15 percent commit suicide(5). Furthermore, bipolar disorder is often misdiagnosed, and patients may suffer up to ten years before a correct diagnosis is made(6).
SEROQUEL(R) (quetiapine fumarate) is the #1 prescribed atypical antipsychotic in the United States(10) and has a well-established safety and efficacy profile. In 2004, sales for SEROQUEL reached $2 billion. SEROQUEL has had more than 13 million patient exposures worldwide since its launch in 1997.
ABOUT BIPOLAR DISORDER
Bipolar I disorder consists of recurring episodes of mania with or without depression. Bipolar II disorder consists of recurring episodes of depression and hypomania, a milder form of mania(8). In the long term, patients with bipolar I disorder spend three times longer in the depressed state than in mania. Patients with bipolar II disorder have traditionally been difficult to treat as they spend almost forty times longer in the depressed state than in mania(9). Without appropriate treatment, patients usually suffer for a lifetime with periods of wellness and functioning punctuated by severe episodes of illness. Both men and women are equally at risk for this illness, which most often emerges in adolescence or young adulthood and recurs throughout life(8).
IMPORTANT SAFETY INFORMATION
SEROQUEL is indicated for the treatment of acute manic episodes associated with bipolar I disorder, as either monotherapy or adjunct therapy with lithium or divalproex, and the treatment of schizophrenia. Patients should be periodically reassessed to determine the need for continued treatment. It is recommended that SEROQUEL be taken in divided doses twice daily. SEROQUEL is not currently approved for the treatment of the depressive phase of bipolar disorder.
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 is not approved for the treatment of patients with dementia-related psychosis.
Prescribing should be consistent with the need to minimize the risk of tardive dyskinesia. A rare condition referred to as neuroleptic malignant syndrome has been reported with this class of medications, including SEROQUEL.
Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated with atypical antipsychotics, including SEROQUEL(R) (quetiapine fumarate). 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 during treatment. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing.
Precautions include the risk of seizures, orthostatic hypotension, and cataract development.
The most commonly observed adverse events associated with the use of SEROQUEL in clinical trials for schizophrenia and bipolar mania were somnolence, dry mouth, dizziness, constipation, asthenia, abdominal pain, postural hypotension, pharyngitis, SGPT increase, dyspepsia, and weight gain.
For full Prescribing Information for SEROQUEL, please visit the Web site http://www.seroquel.com.
ABOUT ASTRAZENECA
AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of prescription pharmaceuticals and the supply of healthcare services. It is one of the world’s leading pharmaceutical companies with healthcare sales of over $21.4 billion and leading positions in sales of gastrointestinal, cardiovascular, respiratory, oncology and neuroscience products. In the United States, AstraZeneca is a $9.6 billion healthcare business with more than 12,000 employees. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.
For more information about AstraZeneca, please visit: http://www.astrazeneca-us.com.
This press release contains forward-looking statements with respect to AstraZeneca’s business. By their nature, forward-looking statements and forecasts involve risks and uncertainties because they relate to events and depend on circumstances that will occur in the future. There are a number of factors that could cause actual results and developments to differ materially. For a discussion of those risks and uncertainties, please see the company’s Annual Report/Form 20-F for 2004.
References
* Depression scores were measured by the Montgomery-Asberg Depression Rating Scale (MADRS).1a The MADRS scale measures the severity of a number of depressive symptoms including mood and sadness, tension, sleep, appetite, energy, concentration, and suicidal ideation.(7) The MADRS score decreases as depressive symptoms improve. Remission was defined as a MADRS score of < / = 12. In BOLDER I, mean change in MADRS scores were at week eight from baseline (-)16.7 for SEROQUEL 600 mg and (-)16.4 for SEROQUEL 300 mg vs. (-)10.3 for placebo; (p<0.001).1d The corresponding mean changes in BOLDER II were (-)16.0,(-)16.9, and (-)11.9, respectively (p<0.001).
(1) Data on file, DA-SER-35
(2) Hirschfeld et al. Screening for Bipolar in the Community. J Clin Psychiatry. 2003;64:53-59.
(3) Judd LL, Akiskal HS, Schettler PJ, et al. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry. 2002;59:530-537.
(4) Depression and Bipolar Support Alliance (DBSA), 730 N. Franklin Street, Suite 501, Chicago, Illinois 60610-7224. Introduction to Depression and Bipolar Disorder. Available at: http://www.dbsalliance.org/PDF/IntroBrochureC2.pdf. Accessed December 7, 2005.
(5) Hawton, et al. Suicide and Attempted Suicide in Bipolar Disorder: A Symptomatic Review of Risk Factors. J Clin Psychiatry. 2005;66:693-704.
(6) Depression and Bipolar Support Alliance (DBSA). Facts About Bipolar Disorder. Accessed at http://www.dbsalliance.org/media/bipolarfacts.html. Accessed December 7, 2005.
(7) Lundbeck Institute. Psychiatric Rating Scales. PDF available at: http://www.brainexplorer.org/factsheets/Psychiatry%20Rating%20Scales.pdf. Accessed December 7, 2005.
(8) Kramlinger K. Mayo Clinic on Depression. Rochester, Minn.: Mayo Clinic Health Information, 2001.
(9) Calabrese JR, Keck PE, Macfadden W, et al, for the BOLDER Study Group. A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry. 2005;162;1351-1360.
(10) All atypical prescriptions: Total prescriptions Jan 05 to Oct 05. New prescriptions Sept 04 to Oct 05 IMS Health. National Prescription Audit.
AstraZeneca
CONTACT: Jim Minnick, +1-302-886-5135, jim.minnick@astrazeneca.com; orLynn Gionta, +1-302-885-5672, lynn.gionta@astrazeneca.com, both ofAstraZeneca
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