FDA Considering Future of Rosiglitazone (Avandia)
Updated July 21, 2010
Following an intensive two-day hearing regarding the conflicting data surrounding rosiglitazone (Avandia), a U.S. Food and Drug Administration (FDA) advisory panel voted in late July to keep the drug on the market with the addition of warnings and stricter product labeling.
Of the 20 members who voted not to remove the drug, the overwhelming majority recommended that it include stricter labeling. Half of those votes suggested that rosiglitazone be restricted to prescription only by physicians with special knowledge in use of the drug. Some panelists also indicated that additional patient education is needed. Only three of the panelists voted to keep rosiglitazone on the market without additional product labeling. The 12 members recommending removal of rosiglitazone argued that pioglitazone works just as well without the known added risks of ischemic events.
The panel was also tasked with making recommendations in eight additional areas, including safety of rosiglitazone as compared to pioglitazone and other hypoglycemic drugs. In evaluating whether rosiglitazone presents greater risk compared to non-thiazolidinedione (TZD) diabetes drugs and pioglitazone, the panel voted 18-6 in favor of the notion that sufficient evidence exists to support an increased risk of ischemic cardiac events with rosiglitazone as compared to non-TZDs. Nine voting members were unable to make a decision on this specific point. The panel also voted 21-4 when asked to determine whether rosiglitazone is less safe than pioglitazone. Eight panel members were unable to decide.
In addition to voting on whether or not the drug should remain on the market and specific safety concerns relative to comparable drugs, the panel was charged with recommending whether or not TIDE, the ongoing international trial designed to compare rosiglitazone to pioglitazone with respect to risk of MI, should continue. In a 20-10 vote, the panel recommended that TIDE carry on (one panelist did not vote and another two were no longer present at the FDA meeting).
Though the FDA panelists failed to reach a unanimous consensus on any of the nine recommendations, they agreed the available data are confusing and additional information is needed. They also seemed to agree that many flaws exist in the data presently available.
"Based on the panelists' comments, there were no easy answers here," said ACC President Ralph Brindis, M.D., M.P.H., F.A.C.C., in a statement following the hearing. According to Brindis, until there is further evidence, physicians should continue working with their patients on a case-by-case basis to determine risks and benefits of rosiglitazone in considering available treatment alternatives.
The meeting marked the second time the FDA convened a panel to review data on rosiglitazone. The first advisory panel was held in 2007 following a publication in The New England Journal of Medicine linking the drug to heart disease risks. At that time, panelists determined that the drug should stay on the market and recommended the addition of a black box warning indicating that rosiglitazone should not be used for patients requiring insulin, patients with a history of coronary artery disease, congestive heart failure or long-term users of nitrates. To underscore the difficult nature of the task at hand, many of the same experts who voted to keep rosiglitazone on the market in 2007 voted to either remove or restrict the drug at this time.
To date, the FDA has not made a final decision on the fate of rosiglitazone. However, the agency on July 21 ordered new enrollment in the TIDE trial to stop. Patients already enrolled in the trial may continue to participate. "This pause in enrollment will give clinical trial investigators and patients time to learn about the data presented to the FDA Advisory Committee and the Committee's recommendations," said Ellen Strahlman, M.D., GlaxoSmithKline's chief medical officer, in a statement.
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