AstraZeneca has announced the submission of a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) for Seroquel XR (quetiapine fumarate) extended-release tablets to seek approval for the treatment of generalised anxiety disorder (GAD), including maintenance of antianxiety effect. It is the first time approval has been sought for an atypical antipsychotic medicine in GAD.
The submission is based on a robust clinical development programme involving more than 3,000 patients. In the data presented, significantly greater symptom improvements were seen in patients treated with Seroquel XR compared to those treated with placebo, in short-term and maintenance treatment, with safety and tolerability consistent with the known safety profile of quetiapine.
GAD, which affects approximately 6.8 million adults in the US, is characterised by persistent anxiety, exaggerated worry and tension. GAD is diagnosed when someone excessively worries about a number of everyday problems for at least six months. Several classes of drugs have demonstrated efficacy in the treatment of GAD. Treatment typically includes selective-serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs); however, approximately 30 per cent of patients do not achieve an adequate response to short-term treatment. Benzodiazepines, commonly prescribed antianxiety medications, may be used for the rapid relief of anxiety symptoms, but long-term use of these agents is not generally recommended.
The GAD submission is based on four phase III efficacy and safety studies. Three short-term, multicentre, double-blind, randomised, placebo-controlled studies compared the safety and efficacy of Seroquel 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 and study 11 (paroxetine 20 mg daily). 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.
The Seroquel 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.