Health problems

AstraZeneca Seroquel Studies 'Buried,’ Papers Show

AstraZeneca Plc "buried" unfavorable studies on its antipsychotic drug Seroquel, according to an internal e-mail unsealed as part of litigation over the medicine.

The drugmaker failed to publicize results of at least three clinical trials of Seroquel and engaged in "cherry picking" of data from one of those studies for use in a presentation, an AstraZeneca official said in a December 1999 e-mail unsealed yesterday under an agreement between the company and lawyers for patients. The London-based company faces about 9,000 lawsuits claiming it failed to properly warn users that Seroquel can cause diabetes and other health problems.

"The larger issue is how we face the outside world when they begin to criticize us for suppressing data," John Tumas, an AstraZeneca publications manager, told colleagues in the e-mail.

More than 15,000 patients have sued AstraZeneca, claiming the company withheld information of a connection between diabetes and Seroquel use from doctors and patients. Many of the lawsuits also claim AstraZeneca promoted Seroquel, approved by the U.S. Food and Drug Administration for schizophrenia and bipolar disorder, for unapproved uses.

AstraZeneca fell 114 pence, or 4.8 percent, to 2,243 pence in London trading. The shares have declined 20 percent this year.

"AstraZeneca has studied Seroquel extensively and shared all relevant and required data with the FDA -- both before and after the agency approved it as safe and effective," Tony Jewell, AstraZeneca's spokesman, said in an e-mailed statement.

'Acted Responsibly'

"None of the documents can obscure the fact that AstraZeneca acted responsibly and appropriately as it developed and marketed Seroquel," Jewell said.

Seroquel, which generated sales of $4.45 billion in 2008, is the company's second-biggest seller after the ulcer treatment Nexium. AstraZeneca has denied wrongdoing in its handling of the drug and is vowing to fight the lawsuits in court.

The company said today that the FDA asked for more information on its application to expand the use of Seroquel XR to include adults with generalized anxiety disorder, following a similar request in December seeking additional data on the drug for major depression in adults. The agency has scheduled an advisory panel meeting on April 8 to review the drug’s safety and effectiveness, AstraZeneca said on Feb. 25.

The U.K. drugmaker agreed to release more than 100 files with information about the drug yesterday after Bloomberg News filed a motion this month to unseal records in the case.

Unsealed Documents

The company and lawyers for former Seroquel users agreed to unseal thousands of documents just before appearing before U.S. Magistrate Judge David A. Baker in Orlando, Florida, for a hearing on that motion. All federal-court lawsuits over the drug have been consolidated in Orlando.

The drugmaker is urging the judge to continue the confidential designation on nine other files, including some that involve what AstraZeneca told foreign regulators about Seroquel and sales representatives' notes on doctors' meetings. The company's U.S. headquarters is in Wilmington, Delaware.

"The court has a duty to make sure things are not inappropriately kept secret," Baker said at yesterday's hearing.

One unsealed document showed AstraZeneca officials considered Trial 15, one of the studies Tumas described as "buried," to be a problem because it didn’t produce favorable results on the issue of weight gain for patients taking the drug. Gaining weight can be a factor in the development of diabetes.

'Smoke-And-Mirrors Job'

Richard Lawrence, an AstraZeneca official, said in a February 1997 e-mail that the company had engaged in a "great smoke-and-mirrors job" in dealing with U.S. and Canadian investigators on the trial's results.

"Adopting the approach Don has outlined should minimize (and dare I venture to suggest) could put a positive spin (in terms of safety) on this cursed study," Lawrence said in the e- mail. It isn't clear from the e-mail which person Lawrence is referring to.

In his December 1999 e-mail, Tumas said that AstraZeneca had "buried trials 15, 31, 56," and was considering a study listed as COSTAR. Details of the trials weren't specified in the e-mail.

He also noted that "there is growing pressure from outside the industry to provide access to all data from clinical trials conducted by industry."

Tumas chastised colleagues for using favorable data produced by Trial 15 without disclosing the full study results, according to his unsealed e-mail.

"There has been a precedent set regarding 'cherry picking' of data," which was used in "the recent Velligan presentations," he said. "Thus far, I am not aware of any repercussions regarding interest in the unreported data."

'Ethical Behavior'

The publications manager indicated that AstraZeneca had a favorable reputation for engaging in "ethical behavior" when it came to disclosing study results on its drugs.

"We must decide if we wish to continue to enjoy this distinction," Tumas wrote.

"The reporting of the COSTAR results will not be easy," he added. "We must find a way to diminish the negative findings. But, in my opinion, we cannot hide them."

AstraZeneca knew Seroquel was linked to weight gain and diabetes and failed to properly disclose its findings to doctors or patients, plaintiffs' lawyer Ed Blizzard said at a press conference today. "We believe that Study 15 was buried because of the weight-gain findings," Blizzard said.

'Don't Look Good'

Among the unsealed documents was a March 2000 e-mail from Tumas in which he noted a study comparing Seroquel to Risperdal, Johnson & Johnson's rival antipsychotic drug, and Haloperidol, an older, generic antipsychotic medicine, produced data "that don't look good."

The results showed that Seroquel failed to best Risperdal in at least five different categories and only outperformed the placebo used in the study, according to data made public yesterday. Those categories included mood, anxiety and hostility, the documents showed.

Tumas warned colleagues in an e-mail that AstraZeneca officials seemed to be "highlighting the only good stuff" about the study when the overall results showed that Seroquel was "less effective than haloperidol and our competitors."

AstraZeneca also unsealed documents showing that Wayne Geller, the drugmaker’s global safety officer, acknowledged in 2000 that researchers had found some links between diabetes and Seroquel.

Geller, who wrote the company’s "safety position paper" on Seroquel, said in a filing with Dutch authorities that there was "reasonable evidence to suggest that Seroquel therapy can cause impaired glucose regulation including diabetes mellitus in certain individuals."

'Fairly Sizeable'

The drugmaker also found a "fairly sizeable" number of cases where Seroquel users' blood-sugar levels had been affected by the drug, Geller noted in the report, according to the unsealed documents.

In August 2000, AstraZeneca said in a response to the FDA that "preclinical data has provided no evidence that Seroquel treatment in man may be associated with diabetes," according to an unsealed document produced in the lawsuits.

In a May deposition that was unsealed yesterday, Geller said the Seroquel safety paper wasn't his final position on the drug's links to diabetes, but rather a reflection of discussions in 2000 about the drug's attributes.

The statement about "reasonable evidence" on Seroquel's possible links to diabetes was "an artifact of an earlier discussion document" and not a conclusion, Geller said in the deposition.

Zyprexa Settlements

Seroquel is part of class of newer antipsychotic drugs, including Risperdal and Eli Lilly & Co.'s Zyprexa, which studies have linked to an increased risk of diabetes. That research prompted the FDA in September 2003 to require AstraZeneca and other drugmakers to warn doctors of the risks.

Lilly has agreed to pay at least $1.2 billion to settle lawsuits filed by about 31,000 patients who used Zyprexa. The Indianapolis-based drugmaker said last month it would pay an additional $1.42 billion to resolve claims by state and federal officials that it marketed the drug for unapproved uses. Lilly also agreed to plead guilty to a criminal charge.

AstraZeneca officials have vowed to defend the Seroquel cases "on their individual merits" and have refused to settle any claims.

Lawyers for former Seroquel users contend that AstraZeneca knew of Seroquel's risks years before the FDA required a stronger warning.

The first two lawsuits set for trial in federal court in Orlando were dismissed last month when U.S. District Judge Anne Conway determined the plaintiffs couldn't prove Seroquel contributed to their development of diabetes.

First Trial

The first Seroquel trial is set for April in state court in Delaware. AstraZeneca officials have criticized lawyers for former Seroquel users for pushing to have documents in the case unsealed.

"It is not surprising that plaintiffs' lawyers have resorted to these tactics to distract attention from their lack of success on the merits of the claims," Jewell said in his statement.

The case is In Re Seroquel Products Litigation, 06-MD-01769, U.S. District Court, Middle District of Florida (Orlando).

(Published by Bloomberg - February 27, 2009)

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