CardioExchange Archive

In a remarkable climax to a long-running drama, the FDA today lifted major restrictions on rosiglitazone (Avandia, GlaxoSmithKline). The drug has been the subject of  intense criticism and controversy since the 2007 publication of the famous Nissen meta-analsysis that first raised the possibility that the blockbuster diabetes drug might increase the risk of heart attack and cardiovascular death.

The FDA said its actions were “consistent with the recommendations of expert advisory committees.” In June of this year an FDA panel reviewed re-adjudicated data from the RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes) trial and concluded that the trial had not found an elevated risk of heart attack or death associated with rosiglitazone.

“Our actions today reflect the most current scientific knowledge about the risks and benefits of this drug,” said Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, in an FDA press release. “Given these new results, our level of concern is considerably reduced; thus, we are requiring the removal of certain prescribing restrictions.”

As a result of today’s FDA action rosiglitzone will be much easier to obtain. Physicians, pharmacies, and patients will no longer have to participate in the stringent Risk Evaluation and Mitigation Strategy (REMS) program.

The rosiglitazone label will also be revised to reflect the FDA’s changed perception of the drug. The current indication for rosiglitazone is severely limited. The new label will be similar to other available diabetes drugs and will state that it may be used to help control blood sugar in type 2 diabetics.

The FDA also said it was “releasing” GSK “from the postmarket requirement to conduct” the TIDE (Thiazolidinedione Intervention with Vitamin D Evaluation) trial comparing rosiglitazone to pioglitazone and other diabetes drugs. The FDA said it had “concluded that this trial is no longer necessary or feasible.”

The FDA announcement “is about the FDA’s effort to save face,” Steve Nissen told the Associated Press. “A single reanalysis of a trial does not exonerate a drug where all the other data point to increased cardiovascular risks.” He said he does not think that most physicians will now begin to prescribe the drug again.

Harlan Krumholz offered the following comment:

The turn of events is surprising given that no substantial information has been made available since the original decision. I don’t know how we will ever know the truth until GSK completely releases the Avandia trial data at the patient level.”