The popular but controversial diabetes drug Rezulin was pulled off the market yesterday after federal regulators determined it was too dangerous.
At least 500,000 Americans use the medication to treat Type 2 diabetes. But pressure has been building to remove the drug because it was linked to 89 confirmed reports of liver failures, including 61 deaths.
The action came after the FDA had faced heavy criticism for originally approving the drug despite concerns about its safety, and for allowing it to stay on the market after patients began to fall ill.
The controversy over Rezulin also contributed to rising concern that the FDA was approving new drugs too quickly. In response to pressure from Congress and elsewhere that the agency had been too sluggish, the FDA began approving some drugs, including Rezulin, through a "fast-track" process that was originally designed for drugs to treat ailments with no cures.
But in recent years the agency has been forced to withdraw a number of drugs approved this way. Some critics have said the FDA's growing use of fast-track has put the commercial needs of pharmaceutical companies over the safety of patients.
The decision over whether to pull Rezulin had also become highly contentious within the FDA, where several key medical reviewers pushed vigorously for its removal. Several FDA employees have said they were summoned before agency internal affairs officers last week regarding the release of information about Rezulin that the agency considered confidential.
Attempts to reach Parke Davis/Warner Lambert last night were unsuccessful.
When Rezulin was approved in 1997, the drug was eagerly embraced by many diabetics and their doctors as an effective alternative for patients whose condition could not be controlled with existing medications. Rezulin works by increasing the body's sensitivity to insulin, a hormone that helps control blood sugar levels.
But troubling reports of liver failure soon began to emerge, and Britain withdrew Rezulin soon after its approval there. Nonetheless, the American Diabetes Association supported the FDA in not removing Rezulin until last week, when it concluded the two similar drugs--Avandia and Actos--were safer.
Through January of this year, Rezulin had generated sales topping $1.8 billion, making it one of the better selling drugs on the market. Avandia and Actos were approved by the FDA last spring, and neither have shown the same level of liver toxicity as Rezulin.
Janet Woodcock, director of the agency's Center for Drug Evaluation and Research, said the agency acted after it became confident that Avandia and Actos were not causing the same kind of liver damage in patients. Before that the benefits of Rezulin outweighed its risks, Woodcock said.
"The message today is not that there is an emergency, that people should stop taking the drug immediately," Woodcock said. "Patients have known for a long time that Rezulin can cause liver toxicity in some people--they get a sheet about that every time they go to the drugstore. We are asking them now to talk to their doctors about using a different medication."
She said that Rezulin, which is also known as troglitazone, would be removed from pharmacies "within a week or so."
The removal, however, will not necessarily end the Rezulin controversy.
Sidney M. Wolfe, a consumer advocate with the Washington-based Public Citizen Health Research Group, wrote to FDA Commissioner Jane E. Henney last week asking for a "criminal prosecution" of Rezulin's manufacturer for failing to properly report several severe cases of liver toxicity during original clinical testing of Rezulin. A researcher who had worked on the clinical trial wrote to Congress on the subject, saying she was pressured into changing her results.
"The handling of Rezulin is one of the worst things I've ever seen at the FDA," Wolfe said yesterday. "Despite evidence to the contrary, they seemed unwilling to add this to the list of mistakes they've made."
Parke Davis/Warner Lambert has denied Wolfe's allegations in the past.
