U .S. and European regulatory authorities offered diverging opinions on the future of GlaxoSmithKline's type 2 diabetes drug Avandia, which has been linked to cardiovascular side effects. Today, the Food & Drug Administration said it would substantially limit use of the drug, and the European Medicines Agency (EMA) made the more dramatic recommendation to suspend marketing of the drug.
FDA has imposed a risk evaluation and mitigation strategy (REMS) on Avandia that will severely restrict the number of patients on the drug. Under the REMS, new patients can take Avandia only if they cannot control their glucose levels using the panoply of other diabetes treatments on the market. People already taking Avandia can stay on the drug. In either case, patients will need to sign a statement saying they understand the risks associated with the drug.
Janet Woodcock, direct of FDA's Center for Drug Evaluation & Research, said today in a conference call with reporters that roughly 600,000 people are currently taking Avandia, a population she expects will shrink substantially under the new requirements.
According to FDA, there is "substantial alignment" between U.S. and European regulatory agencies on interpreting the Avandia data. EMA's decision to withdraw the drug reflects the lack of monitoring tools at its disposal.
The dual regulatory announcements are the culmination of several years of debate over the risks associated with Avandia. One of FDA's own scientists first warned the agency of potential heart risks in 2006, but the issue didn't come to the public's attention until a year later, when Cleveland Clinic cardiologist Steven Nissen published an analysis of dozens of clinical studies involving Avandia in the New England Journal of Medicine. Nissen's meta-analysis found that patients taking Avandia were 43% more likely to have a heart attack. Sales of Avandia, which brought in $3 billion for GSK in 2006, have since plummeted.
In July, an FDA advisory panel convened to evaluate subsequent studies of Avandia's cardiovascular risk. At the end of its review, 12 of the 33 panelists said Avandia should be withdrawn from the market, 10 voted to restrict its use, and the remainder suggested no changes or a minor revision to its label.
FDA said it decided to keep the drug on the market because of scientific uncertainty about its cardiovascular effects. A large, randomized clinical trial called RECORD seemed to demonstrate that Avandia offered no more of a heart risk than two standard diabetes treatments, metformin and sulfonylurea. But questions over the design of the trial have prompted FDA to require GSK to commission an independent review of patients' records to ensure that no cardiovascular events were missed in the earlier analyses. "We hope that readjudication of the RECORD study will add more scientific information and help inform us after it's complete," Woodcock said.