FDA Advisors Reconsider Safety of Diabetes Drug Rosiglitazone (Avandia)
Cardiovascular risk is longstanding concern (June 5)
Two FDA advisory committees are meeting jointly to revisit a 6-year-old debate over the safety of rosiglitazone maleate (Avandia; GlaxoSmithKline), an oral antidiabetic drug of the thiazolidinedione class. It was originally approved in 1999 for the treatment of patients with type 2 diabetes mellitus.
Among the safety concerns for rosiglitazone is a possible increased risk of myocardial ischemic events, such as angina or myocardial infarction. This risk was discussed at FDA advisory committee meetings held in 2007 and 2010. At the 2010 meeting, the results of the RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes) trial were discussed. This open-label, randomized, study — the only cardiovascular outcomes trial for rosiglitazone — compared rosiglitazone-containing combination therapy with combination metformin/sulfonylurea therapy.
During the FDA’s review of the RECORD data, questions were raised regarding whether all cardiovascular events and deaths were properly captured and interpreted. After the meeting, the decision was made to allow rosiglitazone to remain on the U.S. market, but with restricted distribution. Soon afterwards, the drug was withdrawn from European sales. The U.S. patent on Avandia (rosiglitazone) lapsed in 2011.
The purpose of the current 2-day meeting is to present re-adjudicated results of the RECORD trial and to determine whether further analyses based on the re-adjudication might modify the regulatory decisions made in 2010 for rosiglitazone-containing products.
Rosiglitazone is currently marketed in the U.S. under a Risk Evaluation and Mitigation Strategy (REMS), which includes Elements to Assure Safe Use (ETASU). Committee members will be asked to recommend 1) removal of the REMS with ETASU; 2) continuation of the REMS with ETASU without changes; 3) modification of the REMS with ETASU; or 4) withdrawal of rosiglitazone from the U.S. market.
According to a Reuters report, however, the drug’s developer (GlaxoSmithKine) has said that it has no plans to promote rosiglitazone again, even if the FDA advisory panels recommend lifting restrictions on sales of the drug. No generic drug makers have introduced cheaper versions in the U.S.