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.
The F.D.A. announced that it had ordered Glaxo to end a controversial study comparing Avandia and Actos, made by Takeda. It also ordered Glaxo to conduct an independent assessment of the Record trial, a landmark study of Avandia’s heart effects that an F.D.A. medical officer found was riddled with what he said were unpardonable errors that seriously biased the trial’s conclusions.
In 2007, after a study by Dr. Nissen found that Avandia increased the risk of heart attacks, an advisory committee agreed but voted to keep it on the market.
More studies intensified the controversy, so the F.D.A. held another advisory meeting in July. This time, a majority of experts — many of whom had supported Avandia’s continued sales in 2007 — decided that the drug should either be withdrawn or its sales should be severely restricted. With Thursday’s announcements, the F.D.A. and the European Medicines Agency are following that panel’s advice.
Dr. Clifford J. Rosen, a member of the advisory panel that met in July, said he was gratified that the F.D.A. had followed the panel’s advice, and he said the new guidelines “will protect patients while at the same time allowing those few patients who have benefited from treatment to stay on the drug.”
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. Actos, the last remaining drug in the class, appears safe in part because it seems to affect a different set of genes than either Rezulin or Avandia.
Senate investigators found that GlaxoSmithKline spent years hiding from regulatory authorities clear indications that Avandia increased heart risks. In July, GlaxoSmithKline took a $2.3 billion liability charge related to legal cases involving Avandia and another medicine, Paxil. At the time, investors cheered the news as the company’s attempt to set a ceiling for its liability surrounding the medicine.
But the twin announcements by European and American regulators, along with a string of troubling findings about the company’s conduct by Senate investigators, may increase the company’s legal exposure.
Senator Max Baucus, a Democrat from Montana who helped to spearhead an investigation of Avandia, said he was pleased. “The FDA’s tough new restrictions on the drug will help protect patients,” Mr. Baucus said. By GARDINER HARRIS
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.
The F.D.A. announced that it had ordered Glaxo to end a controversial study comparing Avandia and Actos, made by Takeda. It also ordered Glaxo to conduct an independent assessment of the Record trial, a landmark study of Avandia’s heart effects that an F.D.A. medical officer found was riddled with what he said were unpardonable errors that seriously biased the trial’s conclusions.
In 2007, after a study by Dr. Nissen found that Avandia increased the risk of heart attacks, an advisory committee agreed but voted to keep it on the market.
More studies intensified the controversy, so the F.D.A. held another advisory meeting in July. This time, a majority of experts — many of whom had supported Avandia’s continued sales in 2007 — decided that the drug should either be withdrawn or its sales should be severely restricted. With Thursday’s announcements, the F.D.A. and the European Medicines Agency are following that panel’s advice.
Dr. Clifford J. Rosen, a member of the advisory panel that met in July, said he was gratified that the F.D.A. had followed the panel’s advice, and he said the new guidelines “will protect patients while at the same time allowing those few patients who have benefited from treatment to stay on the drug.”
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. Actos, the last remaining drug in the class, appears safe in part because it seems to affect a different set of genes than either Rezulin or Avandia.
Senate investigators found that GlaxoSmithKline spent years hiding from regulatory authorities clear indications that Avandia increased heart risks. In July, GlaxoSmithKline took a $2.3 billion liability charge related to legal cases involving Avandia and another medicine, Paxil. At the time, investors cheered the news as the company’s attempt to set a ceiling for its liability surrounding the medicine.
But the twin announcements by European and American regulators, along with a string of troubling findings about the company’s conduct by Senate investigators, may increase the company’s legal exposure.
Senator Max Baucus, a Democrat from Montana who helped to spearhead an investigation of Avandia, said he was pleased. “The FDA’s tough new restrictions on the drug will help protect patients,” Mr. Baucus said. By GARDINER HARRIS
