FDA to decide on Avandia’s fate Wednesday

By Dr. Ananya Mandal, MDJul 13 2010

Dr Ananya Mandal, MD

Avandia, a drug used as a treatment for type 2 diabetes was approved for use in 1999. However controversies have surrounded it since 2007 when a Cleveland Clinic cardiologist Steven E. Nissen published a study in the acclaimed New England Journal of Medicine that concluded that the drug significantly increased the risk for heart problems like heart attacks, heart failure and deaths. Thereafter this GlaxoSmithKline drug slipped from its popularity although it was not then withdrawn from the market following a vote from an advisory panel to the Food and Drug Administration (FDA). Following continued conflicts of opinion regarding safety the scientific advisers of the FDA convened in Gaithersburg to evaluate the actual evidence regarding the safety of the drug and will decide upon whether it should be removed from the market or used with warnings.

The hearing Tuesday saw the presentation by FDA's Thomas A. Marciniak related to the critical review of the drug’s safety submitted by the GSK. He pointed out that important safety and risk information was missing from the review. This study funded by GSK, known as the Record was published in 2009 and included 4,500 diabetics on Avandia or other diabetes drugs like metformin or sulphonylureas. The Record followed these patients for an average 4.5 years. It showed that there was no rise in hospitalization or death rates in Avandia consuming group. Marciniak also pointed out mistakes in the study design and the case record forms of the Record. He said the study was “inadequately designed and you can't depend on it for safety.” Of some 100 case record forms that were reviewed he said, there were mistakes in at least eight where the patient’s last date of visit was missing. He said, “If you can't even decide when you last saw the patients what confidence do you have in complex determinations such as [heart attack] or death.”

Ellis F. Unger a deputy director in the FDA's drug division said that the data was too inconclusive to form opinions. He said, “There's no clear picture here and if there were you guys would all be back at home.” Kate Gelperin, also of FDA presented similar safety data from FDA’s review of 21 studies showing that Avandia did indeed raise the risk of heart related deaths in diabetics. FDA drug-safety scientist David Graham was the last to present his recently published study that looked at the outcomes of nearly 230,000 Medicare patients who were treated with Avandia or Actos (a competitor of Avandia – Pioglitazone, used in diabetes). Graham’s study looked into the risk of heart attack, stroke, heart failure, or death and showed that Avandia raised the risk of these conditions by 18%. Graham argued that this drug should be withdrawn from the market.

Murray Stewart from GSK defended the drug showing other independent studies that showed the drug to be safe.

The advisory panel comprising of 33 members will vote on Wednesday to decide upon the fate of the drug in the market. They will also decide upon a fresh independent study that compares Avandia with another diabetes drug. FDA Commissioner Margaret A. Hamburg will make the final decision. She has assured that the drug’s safety will be the sole deciding factor that will guide her decision. Ms Hamburg opened the meeting Tuesday with the advice to the expert panel that went, “follow the science where ever it may lead and the rest will fall into place.”