The FDA Must Review Seroquel Bipolar Depression Indication

I know I'm merely a wee journalist on the West Coast and what I think about things doesn't matter very much to anyone, but the piece I wrote yesterday on a major conflict of interest around AstraZeneca's former Seroquel medical chief speaks to more than just how bizarre Big Pharma's behavior has gotten. It speaks to how bizarre things have gotten in the realms of Big Pharma--sexual relationships with a researcher who wrote positively of the drug along with yet another relationship with a ghostwriter who worked on published Seroquel studies that led to FDA approval of the drug--and just how weird the FDA is. The agency declined to respond to questions about the situation.

So as far as the FDA is concerned, you can pay off whomever you want in whatever fashion you desire and the FDA will approve your drug and won't do a thing to guarantee the data submitted to it about a drug's performance hasn't been fiddled with. That's how it looks at this point.

At a minimum, the FDA needs to review the October 2006 approval of Seroquel for bipolar depression. This was not an approval without consequence for AstraZeneca, despite having earlier approvals for schizophrenia and acute mania in bipolar disorder. In 2005, Seroquel sales were $2.76 billion. Sales hit $3.4 billion in 2006. The year after the bipolar depression approval, in 2007, Seroquel sales rocketed to $4.0 billion and hit $4.45 billion in 2008. That's 62 percent growth in less than four years.

That bipolar depression approval was a goldmine for AstraZeneca, but it had little to do with bipolar and much to do with depression. Last December, the FDA busted AZ for off-label marketing of Seroquel for depression. No sanctions against the company have been announced and the FDA still refuses to answer my inquiries as to what range of possible penalties the company might face. "We'll get back to you on that" has been the agency's basic response to me.

AstraZeneca currently has several applications for new indications for Seroquel currently before the FDA. Three of them are for depression.

Last month, the FDA ordered AZ to change its Seroquel label to warn of rapid weight gain on the drug, but the FDA refuses to tell me what data prompted them to order the change and refuses to offer details of what patients were experiencing. Bizarre.

Based upon former Seroquel medical director Wayne Macfadden's involvement with two women involved with the drug's approval, there are obviously serious questions floating around various studies of this drug and if the FDA is just going to ignore the conflicts, then you've got to wonder what it is exactly that the agency does. If the agency is interested in protecting public health and it already knows the company off-label markets its drug and that its drug cause rapid weight gain, a precursor to diabetes, then why wouldn't it look into the bipolar depression approval?

As it happens, none other than Tufts psychiatrist Danny Carlat agrees with me on how valuable the bipolar depression indication was:

"The drug’s approval for bipolar depression was particularly valuable, because it opened the door to off-label use in garden variety, unipolar depression—-a much bigger market than bipolar depression."

I have no idea how the FDA might resolve the conflict of interest issues around Seroquel--probably by ignoring them and hoping they go away--but for once I think it's time the public and legislators started demanding answers from the agency.