AstraZeneca - Seroquel: FDA panel vote 6:3 for treatment resistant depression

Philly Inquirer reporter Miriam Hill writes:

WASHINGTON - A government panel opened the door a crack yesterday toward allowing AstraZeneca to sell its Seroquel XR more widely, after an emotional meeting that included stories from two families who say their loved ones died after taking the powerful antipsychotic.

The Food and Drug Administration advisory committee recommended the agency approve Seroquel XR for use as an additional therapy in patients suffering from depression who do not respond adequately to their current medications.

AstraZeneca, whose U.S. headquarters are in Wilmington, had asked the panel to approve Seroquel much more broadly, to treat depression and anxiety as a single therapy.
Recommending the broader use would have dramatically expanded the market for Seroquel. The drug is currently approved to treat schizophrenia and bipolar disorder, relatively rare diseases, and generates $4.47 billion in yearly sales.

Depression and anxiety, by contrast, affect 10 percent to 20 percent of the population. Wyeth's Effexor XR, one of the world's top-selling antidepressants, generates about $4 billion in sales annually.

"It's certainly going to help their bottom line, but it's not the great victory they had hoped for," said Daniel Carlat, a Tufts University psychiatrist who was not on the advisory panel. He said companies can use such narrow approvals to market a drug more widely.

Bristol-Myers Squibb, for example, has heavily advertised its schizophrenia drug Abilify in TV ads since winning approval for its use as an add-on treatment for depression.

The FDA could still decide to approve Seroquel for even broader uses, but the agency usually follows the recommendations of its advisory panels.

In a statement, Howard Hutchinson, chief medical officer of AstraZeneca, said, "We are pleased that the committee found Seroquel XR to be effective and acceptably safe for use as adjunctive therapy for treatment of [depression]. . . . We look forward to having further discussions with the FDA."

Panel members, including scientists from outside the FDA and consumer advocates, said Seroquel's risks in depression and anxiety outweighed its benefits. The drug leads to weight gain, and some research suggests it can trigger diabetes and heart problems.

Schizophrenia and bipolar disorder are more serious psychiatric illnesses than depression and anxiety, which seemed to change the risk-benefit calculations for several panelists.

"The risks are fairly well-documented, and I don't think they are acceptable for this use," said Richard Malone, a panel member and Drexel University scientist.

Another member, James Neaton, a biostatistics professor at the University of Minnesota, agreed.

"The bar should be higher," Neaton said. "Twenty-five to 30 percent of these patients would be treated chronically, and the longest study was 48 weeks. I accept the fact that the drug is better than placebo, but the effect is modest, and the cardiovascular risk is uncertain."

AstraZeneca scientists presented reams of data asserting that Seroquel was safe and effective for treating depression and anxiety, but several panelists said they would like to see studies that tracked patients for several years, because some cardiovascular diseases take that long to develop.

Allen Jones, a former fraud investigator with the Pennsylvania Inspector General's Office whose work led to the conviction of a state psychiatrist for taking bribes from drug companies, asked the FDA to force AstraZeneca to release every shred of data on Seroquel. He cited documents uncovered by lawyers suing AstraZeneca on behalf of clients who say they were injured by Seroquel.

Those documents, released in a court case earlier this year, include company e-mails in which AstraZeneca employees discussed "buried" studies and congratulated one another for doing "nice smoke-and-mirrors" jobs on Seroquel data.

Janette Layne believes Seroquel may have contributed to the death of her husband, Eric, who was prescribed the drug, along with several others, to treat the post-traumatic stress disorder he developed after serving in Iraq.

Eric Layne died at home in West Virginia in January 2008 while his wife was pregnant with their second child, Jubilee, who accompanied her mother to yesterday's hearing.

"I am the widow of Sgt. Eric Layne. I found my husband dead when our son, Shamus, was 17 months old," Janette Layne told the committee between her tears.

"In summer of 2007, he began taking Klonopin and Seroquel. He ate excessively and would fall asleep with food in his mouth. He had tremors and was extremely lethargic. His speech was slurred to the point I couldn't tell what he was saying. Eric did not have any of these problems before he took these medications."

She showed a short video of her husband slumped over a table in their home and barely able to respond to her questions on Christmas, shortly before he died at age 29.

Stan and Shirley White, also of West Virginia, testified that their 23-year-old son, Andrew, died suddenly after taking the same drugs Layne did. Some researchers suspect that Seroquel can trigger sudden cardiac death, and the Whites have asked Congress to look into the unexpected deaths of about 40 young members of the armed services.

The Veterans Administration determined that White and Layne died "from combined drug intoxication involving prescribed and nonprescribed medications," and said it could not "draw conclusions about the relationship between medication regimens and these deaths."

"He was told, and I as his mother was told, 'These medications will not harm you,' " Shirley White told the panel. "I trusted the doctors to do what was best for my son, and he died in his sleep."

Source

Read the USAToday report here.