GSK’s diabetes drug will be allowed to remain on the market with restrictions due to cardiovascular safety concerns.
FDA announced today that rosiglitazone (Avandia—GlaxoSmithKline) will be available only under “significant” restrictions due to data that indicate increased cardiovascular risks. The drug will be available to new patients only if they are unable to achieve glucose control on other medications and cannot take pioglitazone (Actos—Takeda), the only other thiazolidinedione currently available.
The agency will require GlaxoSmithKline to develop a Risk Evaluation and Mitigation strategy for Avandia according to these restrictions. Patients currently using Avandia can continue doing so. Doctors will have to attest to and document patient eligibility; patients will have to review statements describing the cardiovascular risks associated with the drug and acknowledge their understanding of these risks.
Janet Woodcock, MD, Director of the FDA Center for Drug Evaluation and Research, said in a news conference that the agency was pushed to this decision because questions about the safety of Avandia raised by FDA’s earlier meta-analysis have not been answered satisfactorily. She noted that some had called for more aggressive restrictions, but the agency chose a middle ground of action due to “considerable uncertainty aboiut the magnitude of the cardiovascular risk.”
“Within and outside the agency, there is mostly agreement on the facts, but not on how to weigh the evidence, resulting in different conclusions by the experts,” she said. “This reflects the level of uncertainty in the science. … Therefore, as a matter of prudence, we are restricting access.”
FDA also ordered GlaxoSmithKline to convene an independent group of scientists to review RECORD (Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes), the company’s clinical trial studying the drug’s cardiovascular safety. FDA’s review identified potential bias in the identification of cardiovascular events in RECORD, which the agency will ask this group to review.
In addition, the agency called a halt to TIDE (Thiazolidinedione Intervention with Vitamin D Evaluation), a GlaxoSmithKline clinical trial comparing Avandia to Actos and standard diabetes drugs, and rescinded all regulatory deadlines for completion of the trial. FDA cautioned that the agency may take additional actions after the independent reanalysis of RECORD is completed.
The European Medicines Agency (EMA) responded to the rosiglitazone safety concerns by suspending marketing authorization for the drug in the European Union. Margaret Hamburg, MD, FDA Commissioner, noted that the different responses were largely due to the actions available to each agency. She commented that FDA and EMA discussed their respective actions but did not coordinate them and said that there was “substantial alignment” between the two agencies.
