FDA asks for warning on diabetes drugs

The Food and Drug Administration has called for the clearest safety warning on two diabetes drugs, Avandia and Actos, whose health risks have become a focus of congressional concern.

The decision, disclosed Wednesday by the agency's commissioner at a packed House of Representatives hearing, comes more than a year after the agency's safety reviewers strongly recommended 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, Commissioner Andrew von Eschenbach said the agency has asked the makers of Actos and Avandia to carry the more prominent warning, a so-called black box warning, of its heart risks because "despite existing warnings, these drugs were being prescribed to patients with significant heart failure."

The statement said the agency requested the label changes May 23, which was two days after a medical journal 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 Wednesday.

Dr. Rosemary Johann-Liang, a drug safety supervisor for the agency, had said in an interview this week that she was reprimanded last year for advocating the very label change that von Eschenbach said the agency was now asking the drug companies to make. Avandia, a treatment for Type 2 diabetes 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 Pharmaceuticals and Eli Lilly & Company, has also been seen as carrying some risk of problems, including heart failure.

The makers of both drugs said they were discussing the new warnings about heart failure with the agency. "This is generally a process that takes weeks to months," said Dr. Robert Spanheimer, a senior medical director at Takeda.

Democrats on the House panel voiced harsh criticism of the drug agency and von Eschenbach, whom the Bush administration named commissioner in September 2005.

Representative Henry Waxman, a California Democrat who is chairman of the panel, the House Committee on Oversight and Government Reform, said the agency had "dropped the ball" in its oversight of Avandia's safety.

"Avandia is a case study of the need for reform of our drug safety laws," Waxman said. The agency "needs the will, the resources and the authority to be a more effective watchdog of drug safety."

Democrats asked von Eschenbach if he believed his agency needed more authority from Congress to require drug makers to perform safety studies or correct drug advertisements. Von Eschenbach said his agency required more money, not authority. He characterized as "more destructive than constructive" the proposals by some congressional critics to separate the agency's drug approval and drug safety functions.

Some Republicans on the committee criticized Democrats on the panel for making too much of uncertain information about Avandia, a popular diabetes pill that has been taken by an estimated seven million people worldwide.

Representative Virginia Foxx, Republican of North Carolina, said she was concerned that those studying the drug had spoken to Democrats on the committee but not to anyone at the drug agency.

"I'd like members of the press to investigate what members of Congress knew about this" and whether those members joined some agency staff members and others "to create maximum embarrassment to the agency," Foxx said.

Representative Darrell Issa, Republican of California, said the committee was coming dangerously close to "politicizing science." And he closely questioned Dr. Steven Nissen, a cardiologist at the Cleveland Clinic whose May 21 article in The New England Journal of Medicine questioned 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," Issa said.

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 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, Buse said. "I was characterized as a liar."

source:www.iht.com