FDA panel votes to keep rosiglitazone on market, but wants label changes

An FDA advisory panel voted 20 to 12 to recommend that the agency allow rosiglitazone (Avandia, GlaxoSmithKline [GSK]) to remain on the market. However, most panelists want to see tougher warnings on the diabetes drug’s label, according to various media reports.

FDA usually follows the advice of its advisory committees, though it is not bound to do so.

The panel found that the data presented were sufficient to raise significant safety concerns for heart risk in patients with type 2 diabetes compared with other diabetes treatments. Steven Nissen, MD, a cardiologist at Cleveland Clinic, first raised this concern after analyzing multiple studies of rosiglitazone in 2007.

Only three of the panel members who voted that rosiglitazone should stay on the market thought there should be no changes in product labeling.

The other panelists who voted to recommend that GSK be allowed to continue marketing the drug believed changes are needed. Seven panelists said the company should be required to revise its current label to include contraindications for certain patient populations, although they didn’t clarify which patients might fall into the high-risk subgroup. They also favored adding a warning to the label to recommend rosiglitazone’s use only in patients who have already tried another anti-diabetic agent. Ten panelists voted that FDA should restrict prescribing to physicians who have special education in rosiglitazone.

The 12 panelists who voted to take the drug off the market argued that there isn’t a need for rosiglitazone when patients can take pioglitazone (Actos, Takeda Pharmaceutical Co.), which works as well as rosiglitazone but hasn’t been found to present excess ischemic events.

The panel agreed that rosiglitazone is riskier than non-thiazolidinedione (TZD) diabetes drugs and pioglitazone. Members voted 18–6 (with nine members voting that they were unable to make a decision) that there is sufficient evidence that rosiglitazone increases the risk for ischemic cardiovascular events compared with non-TZD drugs.

Panel members voted 21–4 (with eight members unable to decide) that rosiglitazone is less safe than pioglitazone.

The committee reached its decision after 2 days of presentations and discussions on GSK’s trial data, which panelists said was difficult to interpret.

The panel spent hours reviewing several interpretations of the RECORD trial, which the company has used to defend the cardiovascular safety of rosiglitazone.

RECORD, an open-label trial, was requested by and designed in conjunction with European regulators. It showed no elevation in the combined end point that includes death, myocardial infarction, and stroke compared with active control (hazard ratio 0.93, 95% confidence interval 0.74 to 1.15, P=0.5).

In a statement following the panel’s decision, GSK said it will continue to work with FDA. “GSK is dedicated to sharing data about its medicines transparently and in a timely manner,” said Ellen Strahlman, MD, chief medical officer of GSK. “We remain fully committed to maintaining best practice disclosure of clinical data to serve the interests of regulators, physicians, and patients.”

According to GSK, rosiglitazone has been studied in more than 50,000 patients, making it one of the most extensively researched diabetes medicines. The company has consistently shared data with FDA and worked with the agency to update the label for rosiglitazone as new data became available.

Janet Woodcock, MD, director of the Center for Drug Evaluation and Research for FDA, said a decision will be made as soon as possible. She did not offer a time frame.