"A Very Complex, Difficult History for the Agency": The FDA on Rosiglitazone

October 06, 2010

October 6, 2010 (Silver Spring, Maryland) — The storm surrounding rosiglitazone (Avandia, GlaxoSmithKline) has barely abated since the Food and Drug Administration (FDA) allowed the controversial drug to stay on the market, albeit with restricted access, and agency officials are still discussing their decision, saying the glucose-lowering medication represents a "very complex, difficult history" for the agency [1].

In an video interview this week, Dr Joshua Sharfstein, principal deputy commissioner of the FDA, spoke openly about allowing the drug to stay in the market with restrictions, the discontinuation of the Thiazolidinedione Intervention With Vitamin D Evaluation (TIDE) trial, and whether or not the agency can ever provide complete drug safety to the public.

Speaking with Steve Usdin of BioCentury, a news service that reports on biopharmaceutical business and clinical developments, Sharfstein compared the FDA's approach with that of the European Medicines Agency (EMA). In the US, as reported by heartwire , all rosiglitazone-containing medicines are still available with additional safety labeling and restrictions for use, which includes a risk evaluation and mitigation strategy (REMS) program. Sharfstein said that Europe lacks a similar REMS program and as a result came to a different decision regarding rosiglitazone, which was the suspension of the drug's use.

"There weren't what I would call great differences in the approach that we took," said Sharfstein. "It really reflects the regulatory tools that we have. I think both the EMA and FDA were concerned about the cardiovascular risk signals, as was clearly the advisory committee that we had in the US. They [EMA] suspended but did not revoke the approval of the medication. We put these restrictions in place, which are pretty significant restrictions. They don't really have that tool for this kind of circumstance in Europe. So, I think, in judging the evidence, and looking at the regulatory tools we have, they are generally consistent. Our assessment of the evidence was really that this should be used when other drugs don't work."

Rosiglitazone, he added, likely wouldn't have stayed on the US market without the REMS. In Europe, GlaxoSmithKline recently announced that rosiglitazone-containing medicines will no longer be available from October 21, 2010, bumped up from the original November 8, 2010 recall date.

Speaking to the discontinuation of TIDE, Sharfstein told BioCentury that the trial would have been plagued by a daunting informed-consent process, making continued enrollment difficult, but, more important, would not have yielded any relevant information for public health. Candidly, Sharfstein said that while the overall goal of the FDA when approving drugs is the right balance between risk and benefit, the "absolute assurance of perfect safety" is not possible. He added, however, the rosiglitazone story suggests the agency can balance multiple conflicting opinions and provide increased transparency in explaining decisions.