The first data from the SEROQUEL XR™ (quetiapine fumarate) Extended Release clinical development programme in major depressive disorder (MDD) and generalised anxiety disorder (GAD) were presented at the 7th International Forum on Mood and Anxiety Disorders (IFMAD) in Budapest, AstraZeneca announced today. The data showed that patients who received SEROQUEL XR once daily experienced significant reductions in symptom severity compared to those on placebo in each of three trials, which investigated SEROQUEL XR as monotherapy in MDD, adjunctive therapy in patients with MDD with inadequate response to antidepressant therapy, and as monotherapy in GAD. These studies are part of a clinical development programme that involved over 7,000 patients â one of the largest conducted in depression and anxiety. SEROQUEL® and SEROQUEL XR™ are not approved for the treatment of MDD or GAD.
Reductions in symptom severity were measured by improved (lowered) symptom scale scores. Two randomised, double-blind Phase III studies in MDD reported significantly reduced total scores on the Montgomery-Ã sberg Depression Rating Scale (MADRS) after six weeks of treatment with once daily SEROQUEL XR. In the MDD monotherapy study, mean MADRS score was significantly improved for patients receiving SEROQUEL XR 150 mg (-14.81; p<0.001) and 300 mg (15.29; p<0.001) compared with placebo (-11.18). When given as adjunctive therapy in MDD to patients who were experiencing an inadequate response to their current antidepressant treatment, mean MADRS score was significantly improved for patients receiving SEROQUEL XR 150 mg (-15.26; p<0.01) and 300 mg (14.94; p<0.01) compared with antidepressant alone (-12.21). In a third study examining patients with GAD, mean Hamilton Anxiety scale (HAM-A) score was significantly improved after eight weeks of monotherapy for patients receiving SEROQUEL XR 50 mg (13.95; p<0.05) and 150 mg (15.96, p<0.001) compared with placebo (12.30).
Dr Stuart Montgomery, Imperial College School of Medicine, University of London and author of the MDD monotherapy study, said: "These study results are remarkable â all of the doses of SEROQUEL XR examined provided improvements in MDD and GAD symptoms. Results from further studies that are still ongoing will add to our understanding of SEROQUEL XR in these conditions."
In all three studies presented at IFMAD, SEROQUEL XR was generally well tolerated. The most common adverse events across all of the doses examined (50â300 mg/day) were dry mouth (15.9â38.2 per cent), sedation or fatigue (13.2â38.8 per cent), somnolence (16.8â27 per cent) and dizziness (9.2â19.1 per cent). The numbers of patients with blood glucose elevated above 126 mg/dL at study end for SEROQUEL XR 150 mg, 300 mg and placebo, respectively, were 2.9 per cent, 6.3 per cent and 0.9 per cent in the MDD monotherapy and 3.2 per cent, 6.3 per cent and 3.3 per cent in the adjunctive therapy study. In the GAD study the elevation was seen in 1.1 per cent of patients (50mg SEROQUEL XR), 0.6 per cent (150mg SEROQUEL XR) and 1.7 per cent (placebo).
Martin Brecher, Executive Director Medical Science, AstraZeneca, said: "The data are very encouraging and suggest SEROQUEL XR has the potential to provide a new treatment choice in this area particularly among patients who fail antidepressant therapy with existing treatment. The study programme not only covers adjunct treatment but extended also to monotherapy. New therapy options are needed for treating MDD and GAD because currently available antidepressants do not achieve symptom remission in a substantial proportion of patients. Over the coming months and years we will learn more about how far an antipsychotic like SEROQUEL XR may provide a new option for these patients. AstraZeneca plans regulatory submissions in 2008."
Recently presented data may help to explain the study data in MDD and GAD alongside SEROQUEL®âs known efficacy in bipolar depression. A pre-clinical study used brain imaging with positron emission tomography (PET) to investigate the mechanism of action of SEROQUEL® in non-human primates. SEROQUEL (quetiapine fumarate), both directly and indirectly (via its major active metabolite norquetiapine), was found to target the dopamine D2 and the serotonin 5-HT2A receptors in the brain at blood concentrations similar to those during treatment with clinically recommended doses of SEROQUEL in humans. Additionally, SEROQUELâs major active metabolite norquetiapine was shown to target NET - the transporter for norepinephrine (noradrenaline). Inhibition of NET elevates norepinephrine (noradrenaline) levels in specific areas of the brain, an effect that is associated with antidepressant action.
Launched in 1997, it is estimated that SEROQUEL has been prescribed to more than 25 million patients worldwide. It is approved in 88 countries for the treatment of schizophrenia, in 77 countries for the treatment of bipolar mania, and in 11 countries including the USA for the treatment of bipolar depression. Global sales of SEROQUEL for the first nine months of 2007 were $2.94 billion, an increase of 15 per cent on the same period of 2006. SEROQUEL XR was launched for the treatment of schizophrenia in the US in 2007, and its clinical development programme and planned regulatory filings extend through bipolar disorder to major depressive disorder (MDD) and generalised anxiety disorder (GAD).
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SEROQUEL XR™ and SEROQUEL® are trademarks of the AstraZeneca group of companies.