By Rob Stein
Washington Post Staff Writer
Thursday, September 23, 2010; 9:38 PM
The diabetes drug Avandia will be pulled from the market in Europe and will only be available in the United States under tough new restrictions, regulators said Thursday in an unusual coordinated announcement.
The Food and Drug Administration and European Medicines Agency took the parallel actions after concluding there was significant evidence that the risk that Avandia could cause heart attacks and strokes outweighed the medicine's benefits for most patients.
Under the decisions, Avandia will be unavailable in Europe and U.S. patients will be allowed to take Avandia only if they are unable to control their blood sugar with other drugs. Doctors prescribing Avandia will have to justify the decision. Patients already taking the drug who want to continue will have to sign statements that they understand the risks. In the United States, about 600,000 diabetics take Avandia; the number is expected to decline significantly.
The highly anticipated decision, which will take effect in the next few months, marks the culmination of a long, bitter debate. Once the world's most popular diabetes drug, Avandia became the focus of disagreement over its safety and came to represent concern over the pharmaceutical industry's trustworthiness and the FDA's ability to police drug safety.
Although the FDA pledged to be tough on safety, the Avandia case created a dilemma. Scientists inside and outside the agency were divided about how to balance the drug's risks with the needs of diabetics, who often must try several different medications.
"The FDA is taking this action today to protect patients, after a careful effort to weigh benefits and risks," said Commissioner Margaret A. Hamburg. "We are seeking to strike the right balance."
Although some consumer advocates said the move fell short, some of the drug's most vocal critics indicated they were satisfied.
"The decisions today . . . bring an end to one of the worst drug safety tragedies in our lifetime. By severely restricting access to Avandia, the FDA is ensuring that only a few individuals in America will continue to take this drug," said Steven E. Nissen, the Cleveland Clinic cardiologist who first raised questions about Avandia's safety.
But Nissen added that the action took too long.
"In the aftermath of the demise of Avandia, it is essential to fully investigate what went wrong with the regulatory process to prevent this type of tragedy from endangering patients in the future," Nissen said.
U.S. and European officials said they had been in close contact throughout their respective reviews - a sign of a more collaborative relationship between the agencies that has been in place since 2003 in part because of the globalization of the pharmaceutical industry. The difference in final outcomes reflected a combination of factors, including differences in regulatory processes, officials said. They coordinated their announcements to try to avoid confusion among patients.
It would not have been practical, for example, for the European agency to implement throughout Europe the kind of program the FDA has demanded. At the same time, the European agency stopped short of taking the most drastic action possible, which would have been a complete revocation of the drug's approval. Instead, officials recommended suspending the approval, leaving open the option of reinstating the drug if further data emerge.
The American Diabetes Association and others praised the U.S. decision as a reasonable compromise, but some consumer advocates condemned it.
"The Food and Drug Administration again caved to industry pressure," said Sidney Wolfe, director of Public Citizen's Health Research Group. "Too many people could still be exposed to this dangerous product."
The FDA also ordered the company to convene an independent group of scientists to review a key study the company conducted known as Record. The study, which compared the safety of Avandia to standard diabetes drugs, came under criticism that GlaxoSmithKline had misinterpreted its data.
In addition, the agency halted another company study known as Tide, which compares Avandia to Actos, another drug in the same class, and to standard diabetes drugs. The company hoped the study would prove Avandia's safety and effectiveness. But critics deemed the study unethical because of the drug safety concerns.
The FDA's decision came after outside advisers in July delivered a mixed verdict about Avandia. After a review of the information, including conflicting analyses by FDA scientists, a significant number voted to recommend that Avandia be pulled from the market but a majority urged keeping it available with restrictions and warnings.
Avandia, approved in 1999, quickly became the world's most popular drug to treat Type 2 diabetes, the most common form of the disease, which is increasing rapidly because of the obesity epidemic. But in 2007, Nissen published a study based on information the company was forced to make public and concluded that the drug significantly increased the risk of cardiovascular problems, the leading cause of death among diabetics. Avandia's sales plummeted, and the FDA issued strong warnings about the drug's safety. After a panel of advisers voted to keep the drug on the market later that year, the FDA decided not to pull it.
Critics have said that the decision illustrated the agency's failure to protect the public from dangerous drugs, especially after high-profile safety concerns about the painkiller Vioxx and other medications.
Since then, additional evidence accumulated about the drug's risks, as well as allegations that GlaxoSmithKline knew about the dangers but hid them from regulators and the public. The company has denied the allegations and has defended the drug's safety.
In a statement, GlaxoSmithKline's chief medical officer, Ellen Strahlman, said the company "continues to believe that Avandia is an important treatment for patients" but would work with the regulatory agencies to implement their decisions. The company's stock fell slightly to $39.43.
"It's good the FDA is taking action to ensure that's the case," said Sen. Charles E. Grassley (R-Iowa), who has been investigating how GlaxoSmithKline and the FDA have handled Avandia. "At the same time, the FDA's decision highlights again that the FDA office monitoring drugs after those drugs are on the market remains an unequal player in drug safety efforts."