FDA Not Sure If Diabetes Drug Safe

June 6, 2007 — -- After more than eight years on the market and with a million Americans taking Avandia, the question on Capitol Hill Wednesday was why the Food and Drug Administration still doesn't know whether or not the drug increases the risk of heart attacks.

"Despite additional warnings from outside experts, despite the millions of patients who rely on Avandia to control their blood sugar, and despite the potential risks involved, FDA never required the manufacturer to conduct a thorough postmarket study of its heart risks," said Rep. Henry Waxman, D-Calif., chairman of the House Oversight and Government Reform Committee.

The agency, which admitted it's seriously understaffed, said it is still poring over reams of complicated evidence.

FDA Commissioner Andrew von Eschenbach admitted to the panel, "Up to this point in time we have not had sufficient data of a nature that we could rely upon to draw that conclusion."

"We should not in this country have a medication taken by millions and millions of diabetics that's been approved since 1999 and have the commissioner of the FDA sit in front of Congress today and say I don't know if this drug is safe or not," Dr. Jerry Avorn of Harvard Medical School said of the commissioner's testimony.

GlaxoSmithKline and Avandia have been in the spotlight after the publication last month of a study highlighting some potential risks of the drug. Researchers found that study participants taking the drug had a 43 percent greater risk for heart attack and a 64 percent higher chance of dying from cardiovascular causes than those in a control group who did not take the medication.

Dr. Steven Nissen, one of the co-authors of that article, was also called on the carpet about whether he was seeking the truth or publicity.

"So going to Capitol Hill for a political purpose to get publicity here in a hearing is actually the way it's done?" asked Rep. Patrick McHenry, R-N.C.

"With all due respect, sir, this is about patients, it's not about politics," replied Nissen.

GlaxoSmithKline, Avandia's manufacturer, insists its most recent study shows there is no increased risk of heart attacks. It took out full page ads Tuesday in The New York Times and the Washington Post in support of the drug.

J.P Garnier, the CEO of GlaxoSmithKline, said: "We have put our best foot forward to be transparent about our drug. I think it's fair to say there's a lot of evidence that the drug is safe."

But the company's behavior was under attack on Capitol Hill, too.

The University of North Carolina School of Medicine's Dr. John Buse testified that he was threatened with a possible lawsuit by executives when he raised concerns about Avandia in 1999.

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

In 1999, Buse, fired off a letter to the head of research and development at SmithKline Beecham, the company that later joined with GlaxoWellcome, partly in reaction to "implied threats of lawsuits" by the company because of his stance.

"I may disagree with SB's interpretation of data. I cannot change my opinions in the absence of new data or understanding, in large part because I am not for sale," Buse's letter stated.

"Please call off the dogs," he wrote, referencing the alleged pressure from the company. "I cannot remain civilized much longer under this kind of heat."

Glaxo said it's investigating the alleged incident.

In 2000, Buse sent a letter to the FDA challenging the actions the drug company took, despite warnings.

"I think the FDA has to act forcefully to prevent the rampant abuse of clinical trial data by SmithKline Beecham," he wrote. "I believe that they have overstated the safety of the drug with respect to cardiovascular issues."

But the allegations didn't end there. An FDA supervisor said she was rebuked by the agency last year when she called for strong warnings on Avandia.

"That's what really upsets me, that people have been hurt in the meantime -- waiting for this action to happen," said the FDA's Dr. Rosemary Johann-Liang.

Wednesday's hearing is the most recent instance in which the FDA's ability to monitor drug safety has been called into question.

"We've got a lot of drugs on the market for which nobody can really say if they are safe or not because we don't have an adequate safety surveillance system in place," Avorn said.

"And there are other Avandias out there just waiting to happen."

The FDA said Wednesday it wants the maker of Avandia and a similar drug, Actos, to add the strongest black box warning for congestive heart failure. As for the issue of heart attacks, the FDA will take that up at advisory committee meeting at the end of July.