Federal panel suggests limits on drug for diabetes
members split on whether to withdraw or restrict sales of pill linked to heart attacks
GAITHERSBURG, Md. — A federal medical advisory panel recommended Wednesday that the diabetes drug Avandia should either be withdrawn from the market or have sales severely restricted because it increases the risks of heart attacks.
The panel’s votes, taken after two days of intensive scientific discussions, were a blow to GlaxoSmithKline, which makes Avandia. The company argued that Avandia is a safe and needed option in treating diabetes.
But panel members voiced skepticism about the company’s trustworthiness after questions were raised about its clinical trials. And internal company documents showed that the company for years kept crucial safety information about Avandia from the public.
The panel took six votes on a variety of issues, but its most important came near the end of the meeting when asked what the Food and Drug Administration should do. Of the panel’s members, 12 voted that Avandia should be withdrawn; 10 voted that its sales should be restricted and the warnings on its label enhanced; seven voted only to support enhanced warnings on the drug’s label; and three voted that the drug should continue to be sold with its present warnings unchanged. No one voted for a final option,
Continued from A to weaken the label’s present heart warnings.
Dr. Janet Woodcock, director of the drug center at the FDA, said that the agency took the panel’s advice seriously and that it would consider its regulatory options.
The FDA often takes the advice of its advisory panels, but in this case, it was hard to predict what the agency would do, given the split nature of the vote. The agency allowed competing visions to spill out in the advisory hearing — something unheard of just a few years ago, when the FDA nearly always spoke with a single voice.
“We will come to a decision as soon as possible, and we will announce that publicly,” Woodcock said.
Approved in 1999, Avandia helps control blood sugar levels in diabetics by making patients more sensitive to their own insulin. It is one of a class of three drugs, the first of which, Rezulin, was withdrawn because it caused liver damage. The second drug in the class, Actos, made by Takeda, has appeared safe.
Avandia, which was once the biggest-selling diabetes medicine in the world, saw its sales abruptly decline in 2007 after a study by Dr. Steven Nissen, a Cleveland Clinic cardiologist, found that it increased the risk of heart attacks. An advisory committee in 2007 decided that Avandia did increase heart risks but voted to keep it on the market.
Many of the same experts who decided to keep the drug on the market in 2007 voted Wednesday that it should be withdrawn or restricted. Those restrictions could mean that patients would have to apply for special permission to use the drug.
Reactions were as mixed as the vote.
In a statement shortly after the committee adjourned, GlaxoSmithKline noted that a majority of committee members had voted to keep Avandia on the market.
Nissen said the committee’s vote was the best he could hope for.
“Effectively, this drug is gone,” he said.
Dr. Sanjay Kaul, who voted to require stronger warnings, said that the FDA must ensure that Avandia is used far less regularly.
“Make sure this is available as second-line and not as firstline,” Kaul urged.
The FDA generally undertakes programs to restrict a drug’s sales only when a drug offers a specific benefit, something no study has shown about Avandia. Among the ex- amples of drugs the FDA has restricted are Accutane, an acne drug that can cause birth defects, and Lotronex, a drug for irritable bowel disease that in rare instances is fatal. A majority of the committee found that Avandia increased the risk of heart attacks, but a majority also said that studies had failed to prove it increased the risk of death. A majority also decided that if Avandia were to continue to be sold, the company should complete a clinical trial to prove it is safe. But several members said that the vote probably made a trial impossible because patients would not want to risk taking Avandia.
GlaxoSmithKline said it was in the midst of a clinical trial that would test definitively if Avandia causes heart attacks. Several panel members said the trial came too late.
“The best time to do the trial would have been when the first signal about lipids came up way back in the 1990s,” said Dr. Peter Savage, a member from the National Institute of Diabetes, Digestive and Kidney Diseases.
In the 1990s, GlaxoSmithKline decided against just such a study because it feared that the results might hurt sales, according to internal company documents.
Members of a federal health advisory panel voiced skepticism about the trustworthiness of GlaxoSmithKline, which makes diabetes drug Avandia, after questions were raised about its clinical trials.