Healthy Skepticism Library item: 15188

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Publication type: news

Feeley J, Cronin Fisk M.
AstraZeneca Warned Japanese Doctors of Diabetes Link
Bloomberg.com 2009 Mar 2
http://www.bloomberg.com/apps/news?pid=newsarchive&sid=aAmz5tVXPOM4

Full text:

AstraZeneca Plc pushed salespeople to tell U.S. doctors its antipsychotic drug Seroquel didn’t cause diabetes more than two years after warning physicians in Japan of possible links to the disease, internal documents show.

The London-based drugmaker issued a letter to Japanese physicians in November 2002 that said AstraZeneca had received 12 reports that Seroquel users were diagnosed with high blood-sugar levels over a 21-month period, according to company documents unsealed last week in connection with litigation over the drug.

“Since February 2001 when Seroquel started to be marketed, 12 serious cases (including 1 death) of hyperglycaemia, diabetic ketoacidosis and diabetic coma where causality with the drug could not be ruled out have been reported,” AstraZeneca officials said in the letter.

Almost three years later, AstraZeneca sales managers were instructing company representatives to tell U.S. physicians that “the available data has not established a causal link between diabetes and Seroquel,” according to a transcript of an August 2005 voice-mail unsealed last week.

More than 15,000 patients have sued AstraZeneca, claiming the company withheld information about links 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.

Second-Biggest Seller

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.

AstraZeneca officials said today they sent the letter to Japanese doctors at the request of that nation’s regulators.

“Every country has a different regulatory administration with different regulatory standards and requirements,” Tony Jewell, an AstraZeneca spokesman, said in an e-mailed statement. “AstraZeneca marketing companies are required to comply with the rules and regulations of the regulatory authorities in the country in which they operate.”

Sidney Wolfe, director of Washington-based Public Citizen’s health-research group and a member of the FDA’s drug safety committee, called AstraZeneca’s failure to make a similar disclosure to American doctors “irresponsible.”

“They’re depriving doctors and patients of the right to know the downside,” Wolfe said in a telephone interview. “If there’s enough evidence to warn people in Japan, there’s enough evidence to warn people here.”

FDA-Approved Label

Jewell noted that under U.S. law, drug company salespeople are required to use information from “the label approved by the FDA.” AstraZeneca officials contend that Seroquel’s warning label provided “adequate and appropriate information” about possible diabetes-related side effects.

“When first approved, the Seroquel labeling alerted physicians that diabetes mellitus, hyperglycemia, and weight gain had been observed in clinical trials,” Jewell said in his e- mail. “We have continued to update the label on these topics as the science has developed.”

AstraZeneca’s American depositary receipts, each representing one ordinary share, fell 42 cents, or 1.3 percent, to $31.17 at 4:07 p.m. in New York Stock Exchange composite trading. They have declined 24 percent this year.

130,000 Patients

AstraZeneca agreed to release more than 100 files with information about the drug last week after Bloomberg News filed a motion in federal court in Orlando, Florida, to unseal records in the case. All federal-court suits over the drug have been consolidated in Orlando. The letter to Japanese doctors became publicly available when it appeared on the court’s electronic docket on Feb. 27.

In the letter, AstraZeneca officials noted that the 12 diabetes-related cases emerged from 130,000 patients who had taken Seroquel through the end of September 2002. That means only 0.009 percent of those who had taken the drug reported any diabetes-related problems.

Hyperglycaemia is the medical term for high blood-sugar levels. Diabetic ketoacidosis refers to a condition where the human body doesn’t produce enough insulin.

The company advised Japanese doctors not to prescribe the drug for diabetic patients and to ensure that users monitor their blood-sugar levels, according to the letter. Seroquel’s label didn’t advise U.S. doctors to monitor blood-glucose levels until January 2004, Jewell said.

‘Neutralize Objections’

In the 2005 voice-mail, AstraZeneca manager Christine Ney offered the company’s U.S. sales reps information that they could use to “neutralize customer objections to Seroquel’s weight and diabetes profile.”

Ney noted that while “hyperglycemia-related adverse events have been reported in patients taking atypical antipsychotics, including Seroquel, to date the available data has not established a causal link between Seroquel and diabetes,” according to the transcript.

“Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics, including Seroquel,” she said.

Ney also suggested that salespeople “refocus” doctors away from questions about Seroquel’s links to diabetes to its “Trusted Tolerability profile,” according to the transcript.

Lawyers for ex-Seroquel users question whether AstraZeneca had a pattern of giving foreign regulators and doctors more information about the drug’s diabetes links than their U.S. counterparts.

Safety Paper

Plaintiffs’ lawyers point to a 2000 “safety position paper” on Seroquel that AstraZeneca sent to Dutch regulators reviewing the drug for the European Union.

Dr. Wayne Geller, the drugmaker’s global safety officer, said in the paper that there was “reasonable evidence to suggest that Seroquel therapy can cause impaired glucose regulation including diabetes mellitus in certain individuals,” according to the transcript of a May deposition unsealed last week.

AstraZeneca also found a “fairly sizable” number of cases where Seroquel users’ blood-sugar levels were affected by the drug, Geller said in the report, according to the transcript.

“You did not tell the FDA, you being AstraZeneca, that you have a fairly sizable number of diabetes cases, did you?” Scott Allen, a Houston-based lawyer for former Seroquel users, asked Geller, according to the transcript.

“We presented all the data that we had from all sources, including clinical trial sources, including the literature, including postmarketing sources that were contained in this particular document,” Geller said. “So, in answer to your question, I believe we provided them with more than what was provided here.”

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