FDA Panel: Avandia Should Remain on Market

July 30, 2007 — -- A panel of outside experts recommended to the FDA on Monday afternoon that the diabetes drug Avandia should be kept on the market, despite concern over its heart risks.

Though 20 of the 23 panelists agreed that use of the drug increased heart risks for those with diabetes, 22 out of 23 said that the balance between the drugs benefits and risks supported its continued use in the United States.

But nearly all the panelists agreed that the drug's warning label should be strengthened to reflect its potential risks.

Dr. Scott Gottlieb, a resident fellow at the American Enterprise Institute for Public Policy Research and former Deputy Commissioner for Medical and Scientific Affairs for the FDA, said the panel's recommendation in light of the evidence at hand was the proper move.

"Putting additional warnings on the drug label is prudent, given the suggestion that there is an increased risk with this drug," he said. "But it will take additional studies to establish that risk, and so the advisory committee I believe prudently called for additional research."

However, not all agreed that the panel's decision made sense.

"I find the panel's voting confusing and strange," said ABC News Medical Editor Dr. Tim Johnson.

"If you really believe that Avandia increases the risk for a heart attack -- as they voted -- then why would you keep the drug on the market given that there are other drugs available to lower blood sugar? We obviously need better data after drugs like Avandia are approved -- and the data in this case is still confusing."

One prominent FDA expert, Dr. David Graham -- one of the loudest voices calling for the withdrawal of the pain medicine Vioxx in 2004 -- said the drug, which is manufactured by GlaxoSmithKline and used by about 1 million Americans, should be pulled off the market.

But other physicians said the fears about the drug are thus far unsubstantiated and believe that removing it from the market may deprive diabetes patients of effective medication.

Concerns over the drug were first raised in May with an analysis showing a 43 percent increased risk of heart attack in those taking it.

In a hearing held last month, Rep. Henry Waxman, D-Calif., summarized the issue of whether to take Avandia off the market.

"Diabetes is a serious illness, and Avandia is an effective medication for lowering blood sugar," he said. "Sounding a false alarm about the dangers of the drug has the potential to cause serious harm to patients.

"On the other hand, there have been repeated warnings -- from the day of approval forward -- about the potential cardiac risks associated with Avandia. And these should not be ignored."

Avandia Prescriptions Down

Since the Avandia analysis was published, many doctors are wary and have decided not to write new prescriptions. Others say they are going so far as to take their patients who are already taking Avandia off of the drug.

According to the market research firm ImpactRx, Inc., new prescriptions of Avandia dropped from roughly 15 percent of the market before the study's announcement to below 5 percent now.

This means that in mid-May, about one out of every seven new prescriptions for an oral diabetes medication was for Avandia. Since then, this figure has tumbled to less than one in 20.

And the panel's recommendation may have little effect on some doctors' choices for their patients.

"I will not use [Avandia] and I am aware of other physicians who have made that decision," said Dr. Neil Brooks, past president of the American Academy of Family Physicians.

"The information from the FDA is disturbing," he said. "I believe that most physicians will discontinue the use of Avandia. This is especially true since [Actos, another oral diabetes drug] is available and seems to have a better safety profile."

Actos, a drug made by Takeda Pharmaceuticals in the same class as Avandia but with a different chemical makeup, has benefited significantly from Avandia's decline. Actos held a share of roughly 12 percent of new prescriptions before the announcement of Avandia's association with heart attacks and now holds around 22 percent.

Data show that nearly 60 percent of all switches in diabetes medication were to Actos just two weeks after the announcement -- an increase of around 45 percentage points during that time.

Do Benefits Outweigh the Risks?

But while some physicians want Avandia off the market, others say that Avandia is not much different from many other drugs that have side effects. So as long as the benefits outweigh the risks, they say nothing should change.

"I am very worried about how people will interpret these findings," said Dr. Anne Peters, the director of the clinical diabetes programs at the University of Southern California's Keck School of Medicine. "All drugs have side effects. All drugs can kill you. But the diseases we are treating are far more dangerous.

"I think there is much more danger in patients who are well-treated being pulled off medication," she said.

And Gottlieb said focusing too much on the risks of certain useful drugs could turn out to be both expensive and counterproductive.

"I fear that the task of uncovering these kinds of latent risks -- which is the sort of risk Avandia is believed by some to harbor -- the kinds of risks that can only be unmasked with prolonged use of a drug, is going to be much, much harder and more expensive and cause the delay of a lot of potentially useful medicines," he said.

Company Fires Back

As Graham and other researchers made the case for the removal of Avandia from the market, GSK fired its own salvo of studies at the FDA expert panel asserting the drug's safety and benefits.

"We certainly believe that Avandia is an important treatment option for physicians," Mary Anne Rhyne, a spokesperson for GSK, told ABCNEWS.com Monday morning.

The centerpiece of GSK's defense is a company-funded study, the results of which were released after the May analysis. The study, which GSK said took into account data on more than 400,000 type 2 diabetes patients, provides safety evidence contrary to the findings published in NEJM.

The company-funded study "provides strong evidence that Avandia is not associated with the increased risk of heart attack suggested as part of a previously published meta-analysis," according to a statement by the company.

Rhyne said GSK would not respond specifically to Graham's call for the drug to be pulled off the market.

But why the discrepancy between the NEJM analysis and the studies presented by GSK? Rhyne said these contradictions can be explained by a difference in study design.

"The biggest thing is that a meta-analysis is designed to raise questions, while these other studies are designed to answer those questions," she said. "We believe that a long-term clinical trial designed to look at cardiovascular risk is the best way to answer these questions."

Those sentiments were echoed by Dr. John Messmer of the University Physician Group in Palmyra, Pa., who said that an analysis of studies not designed to look at heart attack risk in Avandia patients should not draw any conclusions about it.

"I think the FDA should advise physicians that there is a suggestion of increased cardiac risk and to exercise caution in prescribing it," he said.

"I do not think the FDA should state that Avandia causes heart attacks. There is no proof of that -- just a trend in the data in some studies. It would be ammunition for unscrupulous lawyers to trawl for cases if the FDA makes a bigger deal out of this than it really is."

Messmer, who said he is "very selective" in the way he uses Avandia, added that he feels the drug should be left on the market so that physicians can weight the benefits of the drug on a case-by-case basis.

"Physicians must judge risk versus benefit every day," he said. "Let it be up to us to make the best decision."