F.D.A. to Restrict Avandia, Citing Heart Risk

By GARDINER HARRIS
Published: September 23, 2010

WASHINGTON — In a highly unusual coordinated announcement, drug regulators in Europe and the United States said Thursday that Avandia, the controversial diabetes medicine, would no longer be widely available.

The drug’s sales will be suspended entirely in Europe, while patients in the United States will be allowed access to the medicine only if they and their doctors attest that they have tried every other diabetes medicine and that patients have been made aware of the drug’s substantial risks to the heart. Patients now taking Avandia may continue to do so.

The Food and Drug Administration’s decision shows that the Obama administration is taking a harder line on drug safety issues, even in the face of scientific uncertainty. Along with its announcement, the agency for the first time immediately posted on its Web site internal memorandums from top staff members that in some cases offered entirely contradictory advice. Dr. Margaret Hamburg, the agency’s commissioner, said that passions within the agency had run high on the Avandia decision.

“As F.D.A. commissioner, my job would be infinitely easier if we had consensus and full scientific clarity,” she said.

Dr. Steven Nissen, a Cleveland Clinic cardiologist whose studies highlighted Avandia’s heart attack risks, said that the decision brought an end to “one of the worst drug safety tragedies in our lifetime,” adding that it was “essential to fully investigate what went wrong with the regulatory process to prevent this type of tragedy from endangering patients in the future.”

One study estimated that from 1999 to 2009, more than 47,000 people taking Avandia needlessly suffered a heart attack, stroke or heart failure, or died.

The decision on Avandia signals a new era in the treatment of diabetes, a disease that is reaching epidemic proportions in much of the industrialized world. Because of Avandia, the F.D.A. announced in 2008 that it would no longer approve medicines simply because they help diabetics control blood sugar levels — the standard for more than 80 years. Instead, the F.D.A. now insists that drugmakers conduct trials lasting at least two years to show that their medicines do not hurt the heart and that they improve the quality or length of diabetics’ lives, far tougher tests.

The Avandia story also begins a new and unsettling period for pharmaceutical companies because Avandia’s risks became known only after Dr. Nissen analyzed data from clinical trials that GlaxoSmithKline, the maker of the drug, had been forced to post on its Web site as a result of a legal settlement. Such public postings are increasingly the norm, which means that drugmakers can no longer easily hide or control scientific information about their medicines.

The agency’s decision to order restrictions on Avandia’s sales also demonstrates that the F.D.A. — given new powers over drugmakers and drug distribution in a 2007 law — intends to use those powers. The agency has now ordered that dozens of drugs be sold only with special restrictions.

In explaining why the F.D.A. decided against only adding more warnings to Avandia’s label, Dr. Janet Woodcock, director of the F.D.A.’s drug center said, “We know that labels are often not read.” It was an extraordinary acknowledgment from a veteran of an agency that for decades relied almost exclusively on label warnings to control drug use.

The suspension and restrictions all but ensure that Avandia’s sales — $1.19 billion last year and $3.2 billion as recently as 2006 — will plunge as regulatory authorities around the world are bound to follow with similar restrictions. Avandia was once the biggest-selling diabetes drug around the world, but concerns about heart attack risks have already cut sales. There are about 600,000 people currently taking Avandia in the United States, Dr. Hamburg said at a press conference. “I think the numbers will go down very, very significantly with these new requirements.”

GlaxoSmithKline responded that “the company continues to believe that Avandia is an important treatment for patients with Type 2 diabetes” and is working with the F.D.A. and European regulators “to implement the required actions.” The company promised that it would end Avandia promotions around the world.

The restrictions will take months to put in place. Patients now taking Avandia should continue to do so until they can consult their doctors, said Dr. Joshua Sharfstein, the F.D.A.’s principal deputy commissioner. But he said that doctors should now consider switching patients to other medicines.

European regulators began their own reassessment of Avandia in July after seeing a study of the drug by F.D.A. medical officers and another by Dr. Nissen in advance of a July F.D.A. advisory meeting. Once each agency learned of the other’s impending and similar decision — both were reached independently, Dr. Hamburg emphasized — they decided to coordinate their announcements.

Several consumer groups said that the F.D.A. should have removed Avandia from the market just as the Europeans did.

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