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FDA Approves Quetiapine for Treatment of Acute Mania Associated With Bipolar Disorder

WILMINGTON, Del., Jan. 12 /PRNewswire/ -- AstraZeneca today announced the U.S. Food and Drug Administration (FDA) has approved SEROQUEL as a monotherapy and adjunct therapy with lithium or divalproex, for the short- term treatment of acute manic episodes associated with bipolar I disorder. The approval is based on results of several registration trials for bipolar disorder, which showed SEROQUEL to be well-tolerated and effective in the treatment of manic episodes - excited mental states seen in bipolar disorder that are characterized by impulsive behavior, racing thoughts, pressured speech, and decreased need for sleep. Patients taking SEROQUEL in the registration trials, either as a monotherapy or as an adjunct to divalproex or lithium, showed improvement of their manic symptoms within the first week of treatment. The improvement was statistically superior to that of placebo or placebo plus lithium or divalproex as measured by the Young Mania Rating Scale (YMRS), a common psychiatric measurement tool.

In the monotherapy studies, 77% of patients who responded to SEROQUEL (100 of 208) had achieved remission by day 21.(1) Response was defined as greater than or equal to 50% decrease from baseline YMRS score and remission was defined as YMRS score less than or equal to 12. SEROQUEL also has shown promise in reducing the agitation, hostility and aggression sometimes associated with manic episodes.(1,2) Further, these studies show that SEROQUEL works across a broad range of mood symptoms as evidenced by improvement in key measures of symptoms associated with bipolar mania.(1,2) SEROQUEL also showed a favorable side-effect profile in particular to extrapyramidal symptoms (EPS) and serum prolactin elevation across the entire dose range.

"The new indication for SEROQUEL represents another treatment option for the millions of people who suffer from bipolar mania," said Dr. Trisha Suppes, Bipolar Disorder Research Program Director, University of Texas Southwestern Medical Center. "While results for individual patients may vary, SEROQUEL was well tolerated in clinical trials and represents a new option for the treatment of acute mania associated with bipolar disorder."

SEROQUEL, which has been approved for the treatment of schizophrenia in adults since 1997, is the fastest-growing leading psychotropic medication on the market in the United States.**(3) Since its initial approval for schizophrenia, there have been approximately 21.5 million prescriptions written for SEROQUEL, for more than 5.3 million patients in the United States.(4)

CLINICAL TRIAL RESULTS

A pooled analysis of data from two double-blind, randomized, placebo- controlled trials assessed the efficacy and safety of SEROQUEL monotherapy for the treatment of acute manic episodes in a large cohort of adults with bipolar I disorder. SEROQUEL was given in doses up to 800 mg/day. The primary endpoint was changed from baseline YMRS (Young Mania Rating Scale) total score at day 21 of treatment.(1) Results showed that:

-- After three weeks, 48.1% of SEROQUEL-treated patients achieved a response versus 31.3% of the placebo group (p=0.001). -- After three weeks, 37.5% of SEROQUEL-treated patients achieved remission versus 23.1% with placebo (p=0.002).

In a separate, double-blind, multicenter, randomized, placebo-controlled trial, SEROQUEL, when administered as an adjunct to lithium or divalproex in the treatment of acute manic episodes in 191 patients with bipolar disorder, achieved a significantly greater response rate compared to lithium or divalproex alone (54.3% vs. 32.6%, p=0.0005). The trial also found that the SEROQUEL-treated group had significantly greater response compared to lithium or divalproex alone (50.6% vs. 31.5%, p=0.012) as defined by extent of improvement (much or very much improved) in the Clinical Global Improvement/BP Score. SEROQUEL was well tolerated with an incidence of EPS no different from placebo across the dose range.(2)

"The approval of SEROQUEL in the treatment of bipolar mania demonstrates the commitment of AstraZeneca to providing medicines that help patients with mental illness," said Dr. Jamie Mullen, Senior Director of Clinical Research at AstraZeneca. "SEROQUEL is an excellent example of the company's dedication to finding effective treatments that patients can accept."

SEROQUEL has recently received approval from the Mutual Recognition Procedure (MRP) involving 14 European countries to extend its use to treat mania associated with bipolar disorder. Health authority approvals have also been received in the UK, Italy, Mexico and New Zealand.

ABOUT SEROQUEL

The efficacy and tolerability profile of SEROQUEL is supported by several placebo- and active-controlled clinical trials in patients with schizophrenia and bipolar mania. In studies supporting the approval of SEROQUEL® (quetiapine fumarate) Tablets, there were no differences from placebo across the clinical dose range in the incidence of EPS, including rigidity and difficulty starting and stopping movement, or in elevation of serum prolactin levels.

In both adjunct and monotherapy bipolar mania clinical trials efficacy was demonstrated in a dose range of 400mg/day to 800mg/day. In clinical trials pertaining to schizophrenia, efficacy was demonstrated in a dose range of 150mg/day to 750mg/day.

IMPORTANT SAFETY INFORMATION

Prescribing should be consistent with the need to minimize the risk of tardive dyskinesia (which is often associated with long-term use of antipsychotic agents), seizures, and orthostatic hypotension. A rare condition known as neuroleptic malignant syndrome (NMS symptoms include muscle rigidity, fever, and irregular pulse) has been reported with this class of medications, including SEROQUEL. There have been reports of diabetes mellitus and hyperglycemia-related adverse events associated with the use of atypical antipsychotics, including SEROQUEL.

The most common adverse events associated with the use of SEROQUEL as monotherapy for either schizophrenia or bipolar mania were somnolence (18%), dizziness (11%), dry mouth (9%), constipation (8%), SGPT increase (5%), dyspepsia (5%) and weight gain (5%). The most common adverse events associated with the use of SEROQUEL as an adjunct therapy with lithium or divalproex in bipolar mania were somnolence (34%), dry mouth (19%), constipation (10%), asthenia (10%), abdominal pain (7%), postural hypotension (7%), pharyngitis (6%), and weight gain (6%). When weight gain was defined as an increase in weight of 7% or more from baseline, there was a statistically significant incidence of weight gain in patients receiving SEROQUEL (23%) vs. patients receiving Placebo (6%). The safety and effectiveness of SEROQUEL in pediatric patients have not been established.

ABOUT BIPOLAR DISORDER

Bipolar disorder, which affects about 2.3 million American adults every year(5), consists of recurring episodes of mania and depression.(6) Without appropriate treatment, patients with this disorder 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.(6)

For more information about AstraZeneca, please visit http://www.astrazeneca-us.com/.

** Leading refers to top 3 prescribed. References
1 Jones MW, Huizar K, et al. Quetiapine monotherapy for acute mania associated with bipolar disorder (STAMP 1 and STAMP 2) [poster]. Presented at the American Psychiatric Assn meeting, San Francisco, Calif., May 20, 2003.

2 Sachs G, Mullen JA, Devine NA, Sweitzer DE. Quetiapine versus placebo as adjunct to mood stabilizer for the treatment of acute mania [abstract]. Bipolar Disorders. 2002;4 (Suppl 1); 133.

3 Based on 2002 versus 2001 TRx growth for the top three Atypical Antipsychotic products, NPA Plus, IMS Health.

4 Data on File

5 Kluger K and Song S. Young and Bipolar. TIME, August 11, 2002

6 Kramlinger, K. Mayo Clinic on Depression. Rochester, Minn.: Mayo Clinic Health Information, 2001.

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