Thursday, June 07, 2007

F.D.A. Calls for New Warnings on Diabetes Drugs

WASHINGTON, June 6 — The government’s top drug regulator told a packed House hearing today that the agency had recently decided to put the agency’s most serious safety warning on two diabetes drugs — Avandia and Actos — whose health risks have become a focus of Congressional concern.
The decision comes more than a year after F.D.A. safety reviewers strongly recommended just such a step, and it occurs amid a Congressional investigation into why the agency delayed its warnings about Avandia for years.
In a written statement, the Food and Drug Administration Commissioner, Andrew C. von Eschenbach, said the agency was asking the makers of Actos and Avandia to carry a more prominent warning of its heart risks because “despite existing warnings, these drugs were being prescribed to patients with significant heart failure.”
The statement said the F.D.A. requested the label changes on May 23, which would have been two days after an article and editorial about Avandia’s potential heart risks set off the current controversy. Word of the label changes, however, had not been made public before today.
Dr. Rosemary Johann-Liang, an F.D.A. drug safety supervisor, said in an interview this week that she was reprimanded last year for advocating the very label change that Dr. von Eschenbach said the agency was now asking for.
Avandia, a Type 2 diabetes treatment made by GlaxoSmithKline, has been the focus of most of the recent safety concerns, based on evidence that it can potentially cause heart attacks or other cardiovascular problems. But its closest competitor, Actos, a drug from Takeda Pharmaceutical and Eli Lilly & Company, has also been seen as carrying some risk of problems including heart failure.
Democrats on the panel voiced harsh criticism of the F.D.A. today.
Representative Henry Waxman, a California Democrat who is chairman of the panel, the House Committee on Oversight and Government Reform, said the F.D.A. “dropped the ball” in its oversight of Avandia’s safety. The agency should have insisted years ago that Glaxo test whether Avandia increased the risks of heart attacks, he said.
“Avandia is a case study of the need for reform of our drug safety laws,” Mr. Waxman said. “F.D.A. needs the will, the resources and the authority to be a more effective watchdog of drug safety.”
But some Republican members of the committee criticized Democrats on the panel for making too much of uncertain information about a popular diabetes pill.
Representative Virginia Fox, Republican of North Carolina, said she was concerned that those studying the drug had spoken to Democrats on the committee but no one at the F.D.A.
“I’d like members of the press to investigate what members of Congress knew about this” and whether those members joined with some F.D.A. staff members and others “to create maximum embarrassment to the agency,” she said.
Representative Darrell E. Issa, a California Republican, said that the committee was coming dangerously close to “politicizing science.” And he aggressively questioned Dr. Steven Nissen, a Cleveland Clinic cardiologist who wrote last week’s study questioning the safety of Avandia.
“This does look like in fact that this was a political concoction to anecdotally go after a company, and I object to it,” Mr. Issa said.
As with most hearings involving the F.D.A., members of Congress today sometimes seemed bewildered by some of the technical answers given by witnesses, and several lawmakers stumbled badly over medical terms at the heart of the debate.
The F.D.A. officials themselves appeared confused when Representative Stephen Lynch, Democrat of Massachusetts, asked the three F.D.A. witnesses to look at Avandia’s drug label and find its warning about heart attacks.
“Have you found it yet?” Mr. Lynch kept asking.
Dr. von Eschenbach deferred to Dr. John Jenkins, head of the F.D.A.’s office of new drugs. Dr. Jenkins eventually made reference to a small table in the labeling information.
“That’s it?” Mr. Lynch asked. “You’re not seriously telling me that that’s it.”
Dr. von Eschenbach said that the F.D.A. was in the process of improving the readability of all drug labels.
Representative Diane Watson, Democrat of California, said she had diabetes and had been taking Avandia until her doctor told her that she had developed a heart murmur.
“My doctor said, ‘Get off of Avandia — there are other options out there,’ ” she said.
She told Dr. von Eschenbach that warnings about such heart problems should be prominently displayed on the drug’s label.
“You ought to have heart attack on the label, and I believe I was heading toward just that when I went to my physician,” Ms. Watson said.
Dr. von Eschenbach said that the F.D.A. was studying the data to decide whether to do just that.
Dr. John Buse, an endocrinologist at the University of North Carolina School of Medicine and the incoming president of the American Diabetes Association, said that when he spoke publicly in 1999 about his fears that Avandia might increase heart risks, he was threatened in phone calls from the drug’s maker.
“During those calls, it was mentioned on two occasions that there were some in the company who felt that my actions were scurrilous enough to attempt to hold me liable for a loss in market capitalization” of $4 billion, Dr. Buse said.
“I was characterized as a liar,” Dr. Buse said. “I was characterized as being for sale.”
Dr. Moncef Slaoui, chairman of research and development for GlaxoSmithKline, said in his own statement that he was “extremely disappointed” by editorials published Tuesday in the New England Journal of Medicine. He said that he and the company “strongly believe that the overall safety of Avandia is comparable to other available oral anti-diabetes medicines.”

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