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Apr 13, 2009
 |  BioCentury  |  Regulation

Deflating Seroquel

AstraZeneca plc went into last week's FDA advisory committee meeting asking for an expansion of the labeled indication for its Seroquel XR quetiapine that could have allowed it to promote the drug for conditions that affect tens of millions of Americans. It came away with a recommendation from the Psychopharmacologic Drugs Advisory Committee that FDA widen the label only slightly beyond the current indications of schizophrenia and bipolar disorder, and that the agency and the pharma take steps to prevent a dramatic expansion of the number of patients who receive the drug.

The committee agreed with FDA that AstraZeneca has demonstrated efficacy of Seroquel XR as a monotherapy and adjunctive therapy to treat major depression, and as a monotherapy to treat generalized anxiety. But the committee was concerned about an observational study that demonstrated an association between atypical antipsychotics and sudden cardiac death, as well as the possibility that Seroquel XR causes tardive dyskinesia.

In addition to potential risks, panel members said adverse effects seen in post-market safety databases, especially metabolic effects such as weight gain, hyperlipidemia, and hyperglycemia, indicate Seroquel XR should not be used in a broad population for conditions such as depression and anxiety that can be treated with safer drugs.

The committee revised the questions FDA asked, splitting the question on whether Seroquel XR is safe for major depressive disorder (MDD) and general anxiety disorder (GAD) into separate votes on unrestricted and limited populations, in order to drive home its alarm at the prospect of unfettered use of the drug ("Seroquel Panel Votes," A6).

The committee voted unanimously against a broad label for monotherapy to treat either depression or anxiety. The 6-3 vote that Seroquel XR is acceptably safe as an adjunctive therapy for major depression was predicated on the understanding that it would only be combined with other drugs if those drugs were not effective on their own.

The panel split 4-4 with one abstention on the question of whether Seroquel XR has been shown to be acceptably safe as a monotherapy to treat any patients with MDD.

The committee voted 2-6 with one abstention against the use of Seroquel XR for any patients with GAD. Committee members said they opposed the addition of anxiety to the label because there are a wide variety of treatments available for anxiety and, unlike depression, the condition is not associated with a high risk of suicide.

Development program

FDA approved an immediate-release version of Seroquel for schizophrenia in 1997. The dibenzothiazepine derivative acts as an antagonist of serotonin, dopamine and adrenergic receptors. A label expansion for bipolar disorder was approved in 2004. The extended-release formulation that allows once-daily administration was approved in 2007. About 26,000 patients have been exposed to the two formulations in clinical studies, and 22 million have received the...

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