AstraZeneca Announces European SEROQUEL XR Submission For The Treatment Of Generalised Anxiety Disorder

Main Category: Anxiety / Stress
Also Included In: Psychology / Psychiatry;  Mental Health;  Regulatory Affairs / Drug Approvals
Article Date: 21 Oct 2008 - 2:00 PDT

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AstraZeneca announced its submission of SEROQUEL XR (quetiapine fumarate extended release tablets) to European regulatory authorities seeking approval for both short-term and maintenance treatment of Generalised Anxiety Disorder (GAD). Building on the US GAD submission announced in May this year,1 this is the first time approval has been sought in Europe for an atypical antipsychotic medicine for the treatment of GAD.

The submission is based on a robust clinical development programme involving more than 3,500 patients. Data from the programme were presented earlier this year at the 21st ECNP Congress in Barcelona in September and at the 161st Annual Meeting of the American Psychiatric Association (APA) in Washington, D.C. in May. In the data presented, significantly greater symptom improvements were seen in patients treated with quetiapine XR compared to those treated with placebo in short-term treatment, with improvement observed as early as day 4.2,3 Symptom improvement was shown to be upheld during maintenance therapy.4 Quetiapine XR was generally well tolerated and the safety and tolerability were consistent with the known safety profile of quetiapine.

During their lifetimes, it is estimated between 2.7% and 5.4% of people in Europe will suffer from GAD.5 Characteristic symptoms include persistent anxiety, exaggerated worry and tension, and it is often accompanied by depression or other anxiety disorders.6,7 It also has a substantial negative impact on Health-Related Quality of Life (HRQoL), productivity at work (including absenteeism) and healthcare costs.5

Antidepressants (SSRIs - selective-serotonin reuptake inhibitors and SNRIs - serotonin and norepinephrine reuptake inhibitors) are standard treatments for GAD that are generally effective, but approximately 30 percent of patients treated with SSRIs or SNRIs will have an inadequate response to short term treatment.8 Additionally, antidepressants may have a relatively slow onset of action (2-4 weeks), sometimes requiring combination with a short course of benzodiazepines (BZDs) to achieve initial symptom control; however, long term treatment with these agents is generally not recommended.9

The GAD submission is based on five Phase III efficacy and safety studies. Four short-term, multicentre, double-blind, randomised, placebo-controlled studies (Studies 9, 10, 11 and 15)2,3,10 compared the efficacy and safety of quetiapine 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). Study 15 was conducted in elderly patients. These short-term studies used the Hamilton Rating Scale for Anxiety (HAM-A) as the primary assessment of anxiety symptoms.

Study 12 was a long-term, multicentre, randomised-withdrawal, parallel-group, placebo-controlled, Phase III study that comprised four phases: an enrolment period of up to 28 days, an open-label run-in treatment period of four to eight weeks, an open-label stabilisation treatment period of 12 to 18 weeks, and a randomised-withdrawal treatment period of up to 52 weeks.3 The quetiapine 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 randomisation to an anxiety event.

About Generalised Anxiety Disorder (GAD)

GAD is a syndrome of ongoing anxiety and worry that is typically recognised as excessive or inappropriate and lasts for at least 6 months. People with GAD are usually overly concerned about everyday matters and tend to anticipate disaster. Physical symptoms of the disorder include fatigue, headaches, muscle tension, muscle aches, difficulty swallowing, trembling, irritability, sleep disturbances, sweating and hot flushes.6,7

About SEROQUEL and SEROQUEL XR

In May 2008, SEROQUEL XR (quetiapine fumarate extended release tablets) became the first ever antipsychotic to complete a clinical development programme and be filed with the FDA in the U.S. seeking approval for the treatment of GAD1 - today it is not approved in any country for the treatment of GAD but remains under review by the regulatory authorities in the U.S. A filing for SEROQUEL XR seeking approval for the treatment of major depressive disorder was made in the US in February with the EU filing in June. SEROQUEL XR is not approved for these indications at this time and the applications remain under review by the regulatory authorities.

SEROQUEL XR is approved in 39 countries for the treatment of schizophrenia in adult patients and for maintenance treatment of schizophrenia in adult patients, 10 countries for bipolar mania and 5 countries for bipolar depression. It was launched in the US in 2007 and earlier this month AstraZeneca announced the approval of SEROQUEL XR in the US for the acute treatment of the depressive episodes associated with bipolar disorder, the manic and mixed episodes associated with bipolar I disorder, and the maintenance treatment of bipolar I disorder as adjunctive therapy to lithium or divalproex.

Launched in 1997, it is estimated that SEROQUEL has been prescribed to more than 22 million patients worldwide*. It is approved in 92 countries for the treatment of schizophrenia, in 88 countries for the treatment of bipolar mania, and in 29 countries including the US for the treatment of bipolar depression.

*Estimates based in IMS APLD and Prescription data.

About AstraZeneca

AstraZeneca is a major international healthcare business engaged in research, development, manufacturing and marketing of prescription pharmaceuticals and supplier for healthcare services. AstraZeneca is one of the world's leading pharmaceutical companies with healthcare sales of US $29.55 billion and is a leader in gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection product sales. 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.com

References

1. AstraZeneca Submits sNDA for Seroquel XR™ for the Treatment of Generalised Anxiety Disorder - a First for the Atypical Antipsychotic Class of Medicines. Press Release 8 May 2008. http://www.astrazeneca.com/pressrelease/5392.aspx

2. 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). Presented at the 161st Annual Meeting of the American Psychiatric Association, Washington, D.C., May 2008. Poster Presentation NR3138.

3. Merideth C, Cutler A, Neijber A, et al. Efficacy and tolerability of extended release quetiapine fumarate (Quetiapine XR) monotherapy in the treatment of GAD. Presented at the 21st ECNP Congress, Barcelona, September 2008.

4. Katzman M, Brawman-Mintzer O, Reyes E, et al. Double-blind study of extended release quetiapine fumarate (quetiapine XR) monotherapy for maintenance treatment of generalized anxiety disorder. Presented at the 161st Annual Meeting of the American Psychiatric Association, Washington, D.C., May 2008. Poster Presentation NR3140.

5. Wyrwich KW, et al. A review of the humanistic and economic outcomes in European patients diagnosed with generalized anxiety disorder. Presented at the 161st Annual Meeting of the American Psychiatric Association, Washington, D.C., May 2008. Poster presentation NR3-065.

6. National Institute of Mental Health: Anxiety Disorders. NIH Publication No. 06-3879. Available at: http://www.nimh.nih.gov/health/publications/anxiety-disorders/generalized-anxiety-disorder-gad.shtml Accessed 10 October, 2008.

7. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association, 2000:472-475.

8. Bezerra de Menezes G, Fontenelle LF, Mulolo S, et al. Treatment-resistant anxiety disorders: social phobia, generalized anxiety disorder and panic disorder. Brazilian J Psychiatry 2007;29(Supplement II):S55-60.

9. Nutt D, Argyropoulos S, Hood S, et al. Generalized anxiety disorder: a comorbid disease. European Neuropsychopharmacology 2006;16:S109-S118

10. Bandelo B, Bobes J, Ahokas A, et al. Results from a Phase III study of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with generalised anxiety disorder. Poster presentation at 7th International Forum on Mood and Anxiety Disorders, Budapest, December 2007.

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