New Study Analyses Confirm Once-Daily Seroquel XR Extended-Release Tablets as Effective Treatment for Schizophrenia

--Study Used To Support FDA Approval of SEROQUEL XR--

WILMINGTON, Del., May 22, 2007 /PRNewswire-FirstCall/ -- AstraZeneca today announced that two analyses from a large-scale study that investigated the efficacy of SEROQUEL XR(TM) (quetiapine fumarate) Extended-Release Tablets, a once-daily medicine for the treatment of schizophrenia in adult patients, were presented today at the annual meeting of the American Psychiatric Association (APA). These analyses from the clinical trial data for SEROQUEL XR showed that it was effective versus placebo in patients with an acute exacerbation of symptoms of schizophrenia.(1,2)

On May 17, 2007, the U.S. Food and Drug Administration (FDA) approved SEROQUEL XR for the treatment of schizophrenia in adult patients.

"Both analyses show that SEROQUEL XR was superior to placebo, demonstrating it is another viable treatment option for schizophrenia," said Charles Schulz, MD, Professor and Head, Department of Psychiatry, University of Minnesota Medical School. "These analyses are significant because SEROQUEL XR may provide greater convenience and simplicity in patient treatment plans."

About large-scale study: Study 132

This six-week, double-blind, randomized, placebo-controlled study investigated the efficacy and safety of once-daily SEROQUEL XR. In this study, 588 patients with acute schizophrenia were randomized to receive either SEROQUEL XR at 400, 600, or 800 mg/day, the immediate release formulation of SEROQUEL(R) (quetiapine fumarate) at 400 mg/day (200 mg twice-daily), or placebo. The primary endpoint was assessed using the Positive and Negative Syndrome Scale (PANSS)(+).(1,2)

In the study, SEROQUEL XR was generally well-tolerated. SEROQUEL XR was administered once-daily at fixed doses, with dose escalation conducted over the initial three days (Day 1 = 300mg, Day 2 = 400 or 600mg, and Day 3=400, 600 or 800mg). The immediate release formulation of SEROQUEL was administered twice-daily and escalated from 50 mg/day to 400 mg/day over a five-day period. The most common adverse events seen in the active treatment groups during the trial were somnolence and dizziness. The incidences of adverse events leading to discontinuation were low: 5.3%, 2.7%, and 2.5% in the SEROQUEL XR 400, 600, 800 mg/day groups; 4.9% in the immediate release SEROQUEL group; and 2.5% in the placebo group. Individual extrapyramidal symptoms (EPS)-related adverse events occurred in three patients or less in all treatment groups.(1,2)

    (+) Schizophrenic symptomatology measured on 30-item Positive and Negative

        Syndrome Scale (PANSS) scale. Each symptom was rated on a severity

        scale from 1-7. PANSS positive (7 items), negative (7 items), and

        general psychopathology (16 items) subscale scores were summarized to

        give the PANSS total score.(3)

About a poster presentation entitled: Efficacy of Once-Daily Extended Release

Quetiapine Fumarate in Patients with Acute Schizophrenia

This first analysis of Study 132 evaluated the efficacy of SEROQUEL XR versus placebo in patients with schizophrenia. The primary endpoint was the change from baseline to Day 42 in PANSS total score.(1)

After six weeks, the mean PANSS total score decreased significantly with SEROQUEL XR (400 mg: -24.8, p < 0.05; 600 mg: -30.9, p < 0.001; 800 mg: -31.3, p < 0.001) compared with placebo (-18.8). In addition, PANSS response rates for SEROQUEL XR (all doses) were significantly higher than for placebo (p < 0.05).(1)

About a poster presentation entitled: Efficacy of Once-Daily Extended Release

Quetiapine Fumarate across Symptom Domains in Schizophrenia

In this second analysis of Study 132, the efficacy of SEROQUEL XR was evaluated across a broad range of symptoms in schizophrenia, including positive and negative symptoms as well as symptoms of general psychopathology, aggression, and depression. Efficacy was assessed from the change from baseline to study endpoint (Day 42) using PANSS total score as well as positive symptom, negative symptom, general psychopathology, aggression, and depression rating scores.(2)

At Day 42, there were statistically significant reductions versus placebo with all doses of SEROQUEL XR for the change in PANSS total, positive subscale, general psychopathology subscale, and hostility and aggression scores. Changes in negative symptom and depression scores of the PANSS were statistically significant versus placebo for SEROQUEL XR 600 mg/day and 800 mg/day.(2)

IMPORTANT SAFETY INFORMATION FOR SEROQUEL XR

SEROQUEL XR is indicated for the treatment of 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 XR is not approved for the treatment of patients with dementia-related psychosis. (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 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 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.

Warnings and Precautions also include the risk of orthostatic hypotension, cataracts, seizures, hyperlipidemia, and possibility of suicide attempt. 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%).

Please see the full Prescribing Information including Boxed Warning for SEROQUEL XR available at www.astrazeneca-us.com/cgi-bin/az_pi.cgi?country=us&product=seroquelxr .

IMPORTANT SAFETY INFORMATION FOR SEROQUEL IMMEDIATE RELEASE TABLETS

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 is not approved for the treatment of patients with dementia-related psychosis. (See Boxed Warning.)

Suicidality in children and adolescents -- antidepressants increased the risk of suicidal thinking and behavior (4% vs 2% for placebo) in short-term studies of 9 antidepressant drugs in children and adolescents with major depressive disorder and other psychiatric disorders. Patients 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 is not approved for use in pediatric patients. (See Boxed Warning.)

A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs, including SEROQUEL. Rare cases of NMS have been reported with SEROQUEL. 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 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. SEROQUEL should be prescribed in a manner that is most likely to minimize the occurrence of TD.

Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated with atypical antipsychotics, including SEROQUEL. 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 during treatment. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing.

Precautions include the risk of seizures, orthostatic hypotension, and cataracts. 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%).

Please see the full Prescribing Information including Boxed Warnings for SEROQUEL available at http://www.seroquel.com .

About Schizophrenia

Schizophrenia is a serious brain disorder with symptoms including distorted perceptions of reality, hallucinations and delusions, illogical thinking, and flat or blunted emotions.(4) Schizophrenia affects men and women with equal frequency, but the first signs of schizophrenia typically emerge earlier in men (in late teens or early twenties) compared to women (in twenties or early thirties).(5) Over 2 million American adults -- about 1 percent of the population age 18 and older -- suffer from schizophrenia. Medications are important in the management of symptoms. While there is no cure for schizophrenia, it is a highly treatable and manageable illness. Medications are classified into two categories -- "conventional" and "atypical" antipsychotics.(6)

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 $26.47 billion and leading positions in sales of gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.

In the United States, AstraZeneca is a $12.44 billion healthcare business with more than 12,000 employees. For nearly three decades, AstraZeneca has offered drug assistance programs side by side with its medicines, and over the past five years, has provided over $3 billion in savings to more than 1 million patients throughout the US and Puerto Rico. AstraZeneca has been named one of the "100 Best Companies for Working Mothers" by Working Mother magazine and is the only large pharmaceutical company named to FORTUNE magazine's 2007 list of "100 Best Companies to Work For." In 2006, for the fifth consecutive year, Science magazine named AstraZeneca a "Top Employer" on its ranking of the world's most respected biopharmaceutical employers.

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

The statements herein include forward-looking statements. By their nature, forward-looking statements and forecasts involve risk and uncertainty. For a discussion of those risks and uncertainties please see the company's Annual Report/Form 20-F for 2006.

    References:

    (1) C Schulz, R Kahn, V Palazov, E Reyes, D Meulien, M Brecher, O

        Svensson, HM Andersson. "Efficacy of Once-Daily Extended Release

        Quetiapine Fumarate in Patients with Acute Schizophrenia." Annual

        Meeting of the American Psychiatric Association, 2007, San Diego, CA,

        research poster board NR04.

    (2) C Schulz, R Kahn, V Palazov, E Reyes, D Meulien, M Brecher, O

        Svensson, HM Andersson. "Efficacy of Once-Daily Extended Release

        Quetiapine Fumarate across Symptom Domains in Schizophrenia." Annual

        Meeting of the American Psychiatric Association, 2007, San Diego, CA,

        research poster board NR495.

    (3) Kay et al.  Schizophrenia Bulletin. 1987;13:261-276.

    (4) American Psychiatric Association. Diagnostic and Statistical Manual of

        Mental Disorders (DSM-IV-TR). Fourth Edition.  Arlington, VA, 2000.

        299.

    (5) National Institutes of Mental Health.  The Numbers Count: Mental

        Disorders in America. NIH Publication No. 06-4584.  December 2006.

        http://www.nimh.nih.gov/publicat/numbers.cfm.

    (6) National Alliance for the Mentally Ill: About Mental

        Illness/Schizophrenia fact sheet. Reviewed by Kenneth Duckworth, M.D.:

        February 2007.

CONTACT: Jim Minnick, +1-302-886-5135, , orAbigail Baron, +1-302-885-3578, , both ofAstraZeneca jim.minnick@astrazeneca.com abigail.baron@astrazeneca.com

Web site: http://www.astrazeneca-us.com//

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Posted: May 2007

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