Seroquel

Recently released internal documents and e-mails show that AstraZeneca, a London pharmaceutical company with U.S. headquarters in Wilmington, knew a decade ago that its drug Seroquel caused diabetes and significant weight gain. Seroquel is a second generation atypical antipsychotic that is currently approved by the FDA to treat bipolar disorder and schizophrenia. In an Orlando federal court, where thousands of lawsuits brought by individuals injured by Seroquel have been consolidated, AstraZeneca had repeatedly argued that its documents should remain under seal because they contain proprietary information that could hurt the company if revealed to competitors and could harm the public if taken out of context. However, just hours before the Orlando court was scheduled to hear oral argument on AstraZeneca's request to maintain the confidentiality of a representative sampling of its internal documents, the company agreed to unseal the majority of the documents at issue. Following the hearing, Ed Blizzard told reporters, "Our position was that the public has the right to know."

Many of the released documents show that AstraZeneca was aware that Seroquel caused significant weight gain even before it was approved by the FDA in 1997. Among these documents is a 1997 e-mail written by Seroquel Project Physician, Lisa Arvanitis, in which she contemplated the potential "competitive advantage for SEROQUEL re-weight gain." Arvanitis wrote, "I was really struck by how consistent the data was" from multiple patient studies showing weight gain "is more rapid initially," but continues for at least a year. "It doesn't stop," she wrote. "The other issue of what we tell the sales force is more problematic." Meanwhile, in a memorandum discussing the presentation of data from "Study 15," which compared Seroquel to the first generation antipsychotic drug, Haldol, AstraZeneca commercial strategist, Richard Lawrence, wrote that Lisa [Arvanitis] has done a great "smoke and mirrors job," which "should minimize (and dare I venture to suggest) could put a positive spin (in terms of safety) on this cursed study." Despite having ample data which suggested Seroquel causes significant weight gain, released documents show that AstraZeneca nevertheless promoted Seroquel as having a "favorable weight profile" and as being "weight neutral."

Released documents also show that AstraZeneca was aware as early as 2000 that Seroquel could cause diabetes but failed to share its knowledge with the FDA. Among the documents was an internal "Safety Position Paper" written in August 2000 by Dr. Wayne Geller, AstraZeneca's then Global Drug Safety Physician, in which Dr. Geller concluded, "There is reasonable evidence to suggest that Seroquel therapy can cause impaired glucose regulation including diabetes mellitus in certain individuals." Just weeks later, however, AstraZeneca told the FDA that "preclinical data has provided no evidence that Seroquel treatment in man may be associated with diabetes."

AstraZeneca's documents also show that the company attempted to conceal the health risks created by Seroquel from the prescribing medical community. When physicians asked about the link between Seroquel, diabetes and weight gain, Christine Ney, AstraZeneca's Scientific Alignment Manager, instructed sales representatives to "neutralize customer objections" and "refocus" on the positive by referring to a handy "Weight and Diabetes Sell Sheet." "Thanks everyone and good selling!" Ney said.

In an apparent effort to increase Seroquel sales, AstraZeneca attempted to conceal unfavorable data and publish only positive data on Seroquel. In one released e-mail, Seroquel Publications Manager, John Tumas, expressed his concern that the company had set a precedent for "cherry picking" data, including data from Study 15, had "buried" three studies and were considering doing the same with a fourth study. "The larger issue is how do we face the outside world when they begin to criticize us for suppressing data," wrote Tumas.

Over the past dozen years, AstraZeneca has marketed Seroquel as an effective treatment for schizophrenia and bipolar disorder, selling more than $20 billion of the drug. In 2008 alone, Seroquel sales totaled $4.45 billion. However, some of the recently released documents show that Seroquel may not only be less effective than its second generation competitors, but also less effective than the first generation antipsychotic drugs it was supposed to improve upon. Among the documents is a March 2000 e-mail from John Tumas in which he comments on a study comparing Seroquel to Haldol and other second generation antipsychotics. "The data don't look good," Tumas wrote. "In fact, I don't know how we can get a paper out of this." The results from this study showed that Seroquel failed to beat its competitors in at least five different categories and, in fact, only outperformed placebo (sugar pill).

The recently unsealed documents represent only a small sampling of the millions of pages of documents produced by AstraZeneca in the ongoing litigation. More documents are expected to be unsealed in the near future.