Seroquel Marketing Plan Included “Spinning The Data, aka Lilly”

Plantiffs attorneys allege that AstraZeneca internal documents reveal intense effort to imitate competitors, placate study investigators.

Attorneys representing plaintiffs in Seroquel product liability litigation released more internal AstraZeneca documents, claiming the material shows the company sought to hide the drug's adverse effects and promote it for off-label use.

The documents also give a peek at how the company sought to copy approaches used by Lilly and Janssen in studying their atypical antipsychotics and tried to placate one of its top investigators, who was valued at $500 million by one AstraZeneca employee.

"AstraZeneca spun, skewed and concealed from doctors, patients and sometimes their own scientific investigators" that Seroquel (quetiapine) caused diabetes and significant weight gain in a significant number of people, Edward Blizzard, of Blizzard, McCarthy & Nabers, said in a Nov. 20 press conference call. He was joined by Camp Bailey, of Bailey Perrin Bailey.

In February the attorneys released the first wave of AstraZeneca documents unsealed in Seroquel multidistrict litigation proceedings. That data, they said, showed the company knew of the risk of diabetes and weight gain in 2000 (¹ (Also see "AstraZeneca Internal Seroquel Documents Cite Cherry-Picking, Burying Data" - Pink Sheet, 27 Feb, 2009.)). This time they emphasized materials that they claim show top company officials planned to promote the drug for off-label use to children and the elderly through presentations at scientific events and third party vendors. They plan to release a third set of documents the first week of June.

AstraZeneca appreciates Lilly's ability to "spin" data

Emails released in the most recent batch of documents reveal that AstraZeneca looked to competitors to see how they dealt with investigator initiated trials (IIT). The company commissioned a study in which AstraZeneca staff who had worked for competitor companies were interviewed about how their former employers' handled such trials. In an August 2003 email to Seroquel's global brand team and global product team, Simon Hagger, global brand manager for Seroquel, seemed impressed with how Lilly, which markets Zyprexa (olanzapine) and Janssen, manufacturer of Risperdal (risperidone), ran their IIT programs.

Lilly, he said, has a significantly higher investment in its program than AstraZeneca and is fast and effective in turning studies around. In addition, he said Lilly is "able to spin the same data in many different ways through an effective publications team" and "negative data usually remains well hidden." He recommended that AstraZeneca publications should be "more creative spinning the data, aka Lilly."

As for Janssen, he said "high expectations are set on investigators who publish favorable results but they are well rewarded for their involvement." In addition, he said the company seems "less concerned than Lilly about negative data reaching the public domain."

Lilly's market efforts for Zyprexa resulted in a record-setting $1.4 billion settlement with the U.S. Department of Justice (² (Also see "Lesson from Lilly’s Zyprexa Settlement: Be Proactive In Monitoring Sales Reps" - Pink Sheet, 6 Apr, 2009.), p. 37). By attempting to emulate Lilly's approach, AstraZeneca may have set itself down the same path.

AstraZeneca Faces Many Lawsuits

The U.S. Attorney's Office in Philadelphia is conducting an investigation of AstraZeneca's sales and marketing practices for Seroquel, including off-label promotion. Approximately 34 states are conducting their own joint investigation.

AstraZeneca said it complies with laws and regulations in its interactions with healthcare professionals, including FDA-approved labeling and FDA regulations. "The plaintiffs' lawyers in this case have tried before and we expect will try again to press their claims with sound bites in the newspapers," the company said in a statement. "But, as we've seen repeatedly in the cases prepared for trial to date, when plaintiffs actually have to prove their claims in a court, they cannot.

"As AstraZeneca has repeatedly said, the evidence - looked at fully and fairly - just doesn't back up the allegations that Seroquel was responsible for the plaintiffs' alleged injuries."

Approximately 6,000 product liability cases are pending in multidistrict litigation proceeding in the U.S. District Court for the Middle District of Florida and 9,000 cases are pending in state courts in Delaware, New Jersey and New York. In February the judge overseeing the federal MDL cases granted AstraZeneca's motion for summary judgment in the first two test liability cases, finding that plaintiffs did not have sufficient evidence to establish that Seroquel caused their injuries.

The first trial is scheduled to begin in Delaware state court on June 29. AstraZeneca's motion for summary judgment in that case is pending.

Off-label Efforts

One document highlighted by the plantiffs attorneys is the company's Seroquel PR plan for 2001, in which the AstraZeneca says "aggressive market penetration is required" in several patient sectors, including the elderly - such as those with Parkinson's disease and Alzheimer's dementia - adolescents, and patients with bipolar disease. An October 2002 email from Christopher Maurer, AstraZeneca's senior marketing research manager, advises his colleagues to explore focusing on dementia and treatment-resistant anxiety among primary care physicians.

In 2005 FDA requested a boxed warning on atypical antipsychotics that the drugs are not approved for treatment of elderly patients with dementia and that clinical studies have shown such use was associated with a higher death rate compared to placebo.

Conflict with Seroquel researcher

The flood of documents includes intriguing information about one of AstraZeneca's Seroquel researchers, Michael Reinstein, a psychiatrist at Community Mental Health Services in Chicago. In a November 2001 email, AstraZeneca's Malcolm May, associate sales director in CNS, advised colleagues to be responsive to Reinstein's criticisms about trial protocols and personnel.

Noting that someone named Michael, who was not identified further, had claimed Reinstein "could be worth as much as $500 million dollars to AZ over his career," Malcom said "if he is in fact worth half a billion dollars to AZ, we need to put him in a different category than our other trialists. That means someone who is prepared to answer to his every query, and satisfy any of his quirky behaviors."

"It seems we are annoying possibly our most important single customer, and that is not acceptable," she added. Another AZ letter identified Reinstein and one of his colleagues as the "single largest users of Seroquel in the country."

In an Oct. 23, 2001 letter to AstraZeneca CEO David Brennan, Reinstein and his colleagues at Community Mental Health Services, expressed frustration with the company's promotional practices, which he said enabled Janssen's Risperdal to achieve a higher market share. He also cited the need for studies on higher dosages of Seroquel, and objected to having to pay for airfare, hotel and other expenses when acting as a speaker for Seroquel.

Reinstein had a subsequent luncheon meeting with AstraZeneca staff, which was summarized in a Nov. 1 internal company letter. According to the letter, Reinstein was unhappy that a Seroquel study had not yet been published, did not get along with certain AZ clinical research staff, and had said it was ludicrous that risperidone, which he characterized as "just a dirty drug," had double the market share of Seroquel.

Reinstein apparently was not well received by everyone at AstraZeneca. In an Oct. 30, 2001 communication about the Reinstein letter, Georgia Tugend, market development director for CNS, said the CMHS group "is constantly demanding research grants from us but the quality of their research and poor reputation in the psychiatry community has limited our work with them to retrospective chart reviews or small pilot trials." He added that they have "blatantly threatened to switch their Seroquel patients to [Pifizer's] Geodon (or back to ... Risperdal) if they do not get research funding from AZ."

Another internal communication shows AstraZeneca batted around the idea of asking FDA to approve a claim that Seroquel could reduce suicidal behavior. In a November 2005 email, Wayne Macfadden, former director of clinical research and U.S. physician for Seroquel, discussed draft prescribing information prior to a meeting with FDA. He said two consultants were encouraging in the discussion of whether or not to describe reduction of suicidality in the label, despite not having pre-specified it as an endpoint of interest to FDA.

"We realize the data are not overwhelming and there is not a high likelihood of the acceptance by the FDA of this language," Macfadden stated. "The team's consensus, however, is to proceed, as we believe we a) pass the red-face test and are not making an unreasonable request of the FDA, b) are not trying to force any other data from any other secondary endpoint in the label and c) describing this in the label would be a major area of differentiation from other compounds used to treat bipolar disorder."

-Brenda Sandburg (³ [email protected])