Will the FDA go back on a decision it made years ago? I am referring to a story that has a lot of buzz: whether or not the FDA will take recommendations from its advisory committee and change the restrictions on Avandia (rosiglitazone). Avandia was approved in 1999 and shortly became the top-selling type 2 diabetes medication in the world. In 2010, data from a number of trials convinced the FDA to severely restrict the medication through implementation of a Risk Evaluation and Mitigation Strategy (REMS), while Europe banned it entirely. Following this decision, the FDA required that GSK appoint an independent organization to conduct a re-evaluation, also known as re-adjudication, of the Rosiglitazone for Cardiac Outcomes and Regulations of Glycemia in Diabetes (RECORD) trial.
An advisory committee gathered last month to review the results of the readjudication, which was conducted by the Duke Clinical Research Institute. The result was a majority of panel members favoring the modification or removal of the REMS. At the time of the RECORD trial, there had been a lack of uniform definitions for cardiovascular endpoints. Since then, the FDA has made efforts to create standard definitions for cardiovascular endpoints and methods to collect cardiovascular event data in clinical trials.
The FDA briefing document on the re-adjudication of the trial still points out other limitations of the study such as its open-label, non-inferiority design. In addition, critics have implied that the re-adjudication was also flawed, considering GSK provided Duke with the files that were needed. I am certain pharma is taking notes on many aspects of this controversial case. We are likely to see diabetes on the rise as, well as novel therapies. Companies can determine from situations like this how to effectively assess and present safety data, particularly cardiovascular outcomes in this patient population. The suggestions of the panel are not binding, and time will tell what what role the votes play in the FDA’s decision. It is a shame, though, because regardless of whether Avandia can emerge from its dark shadow, there is no amount of SPF that can protect GSK from the burns it has already endured.
Jessica Cherian, PharmD, RPh, is a clinical adjunct faculty member at Temple University in Philadelphia and is a community pharmacist.