May 22, 2009 -- Did AstraZeneca hide studies that showed its popular anti-psychotic drug Seroquel could lead to large weight gain and diabetes? Did the company illegally try to promote off-label use of the drug?
Those are the contentions of attorneys suing the company who Wednesday released dozens of documents that had previously been under court seal.
Houston attorney Ed Blizzard said the documents "show that Seroquel was not effective and had serious risks."
"AstraZeneca knew those facts but spun, skewed and concealed that data from doctors, patients, and sometimes their own scientific investigators," Blizzard contended.
The first case of about 15,000 patients who are suing AstraZeneca -- most claiming Seroquel led to diabetes -- is expected to go to trial next month. AstraZeneca will also go before the U.S. Food and Drug Administration next month to seek approval for Seroquel use among children and adolescents.
But attorneys suing AstraZeneca suggested this week that documents showed the company knew much more about Seroquel -- approved for schizophrenia and bipolar disorder in adults -- than it told the public.
Attorneys say, for instance, that the company promoted Seroquel as "weight neutral" despite a study that showed significant weight gain after 18 months on the drug.
In a 2001 e-mail, then AstraZeneca psychiatrist John Travers said, "These data also suggest to me that the concept of "weight neutrality" are not supported by these data." He argued that presentations should include the data.
Another e-mail discussed "trial 41," which the liability attorneys say showed an extended-release version of Seroquel was no better than a placebo.
"We are under clear instruction from the highest level within AstraZeneca at this time not to discuss details surrounding trial 41 with any external customers," Simon Hagger, then AstraZeneca's global brand manager for Seroquel, wrote in the e-mail.
AstraZeneca spokesman Tony Jewell Wednesday accused the lawyers of attempting to try the case in the media and notes the first two cases were dismissed for lack of evidence.
"AstraZeneca conducted 118 studies (on Seroquel)," Jewell told ABC News. "We shared all of the required data with the FDA both before and after it was approved. We stand by our clinical research."
FDA spokeswoman Sandy Walsh said in an e-mail today that Seroquel's label has been updated as new information dictates, and that AstraZeneca has never resisted any of those efforts.
"The Seroquel label from the very first approval reflected metabolic side effects, and that language has been strengthened over the years as new data became available," she said. "Like all other atypical anti-psychotic drugs, Seroquel got a very strong Warning statement about potential diabetes in 2004."
"It is important to distinguish between what is said in internal company documents reflecting internal disagreements about how to present and characterize certain findings and what a company actually provides to FDA," Walsh said. "There is no evidence that at any point AstraZeneca withheld important data from the FDA. If there was such evidence, that would be important, but we are not aware there is such evidence."
Doctors Sound Off on Release of Seroquel Documents
Some in the medical community are skeptical about the release of the internal AstraZeneca documents.
"Oh, please," said Dr. Henry Miller at Stanford University's Hoover Institution in California. Allegations based on selective leaks from plaintiff lawyers?"
Miller has no financial ties to AstraZeneca, but he was an expert consultant to the law firm that defended Merck during litigation over the pain drug Vioxx.
"If the FDA-approved labeling lists all the relevant side effects, what, exactly is the problem?" Miller asked. "What was the company supposed to do -- advertise the known side-effects of the drug in 10, one-minute commercials during the Super Bowl?"
Still other medical professionals had a different reaction.
David Kroll, professor and chairman of the department of pharmaceutical sciences at North Carolina Central University's Biomanufacturing Research Institute and Technology Enterprise, said that given the reports of the case, AstraZeneca's alleged actions would be "unconscionable and unethical" if true.
"This episode is one in a long string of others that have eroded public faith in the pharmaceutical industry and make it difficult for us who try to communicate real-world risks and benefits of drugs," Kroll said.
Dr. John Abramson, clinical instructor at Harvard Medical School in Boston and author of "Overdosed America," believes there should be stiffer penalties for drug companies if they are indeed found to be withholding information.
"As these cases have unfolded, whether it's Vioxx or Neurontin or Bextra, what we've seen is that there have been some sizeable settlements in civil litigation ... as a consequence of alleged fraudulent marketing," Abramson said. "But, to date, these settlements have not been large enough to exceed the costs of not doing business."
Abramson said he is not familiar firsthand with the Seroquel lawsuit, but is serving as a plaintiff's expert witness in other lawsuits involving anti-psychotic drugs.
"One thing that I personally see repeatedly in the litigation work that I do is that safety issues will emerge and there will be a delay in bringing those safety issues forth," he said.
Abramson said the important issue at play is what the company does during this period of delay. He said problems arise when the manufacturer continues to advertise the drug in question in a positive light, even as they are in possession of information that suggests the potential harms of its product.
"The longer this information is delayed and in its place positive information is being supplied, the bigger a hole is dug in terms of coming to an accurate understanding of the risk-benefit ratio of the drug."
Attorneys suing AstraZeneca also revealed another e-mail to the Seroquel global brand team from Hagger Wednesday that compares AstraZeneca's strategies with those at other drug companies. He wrote AstraZeneca needs to make sure publications are "more creative spinning the data, aka Lilly."
The document notes that drug giant Eli Lilly is able to spin the data in many ways and that "negative data usually remains well hidden."
Indianapolis-based Eli Lilly defended itself today against that charge.
"While we have no comment on the memo itself, we will say that at Lilly, we have long maintained a policy of open, transparent disclosure of clinical trial results, regardless of outcome," Eli Lilly spokeswoman Marni Lemons said in a statement today.
Off-label use of Seroquel was also the subject of scrutiny, with one AstraZeneca document explicitly stating a goal of "broader Seroquel use on and off label."
AstraZeneca's Jewell denied the company tried to promote off-label use, noting the documents do not demonstrate off-label promotion.
"The documents demonstrate AstraZeneca's commitment to pursuing new FDA-approved indications for Seroquel," he said.
Still, Kroll of North Carolina Central said he worried about the damage these documents could do for patients who truly need the medication. He worried that left untreated, bipolar disorder could lead patients to suicide attempts or violent behavior which are "much more damaging than the potential side effects."
"My biggest concern also is that the controversy may overemphasize the risks of Seroquel and cause people who truly need the drug to stop using it and have a return of their very serious symptoms," he said.