FDA Panel Recommends Backing Off Avandia Restrictions

An FDA advisory panel voted last week to recommend that the federal drug regulators ease restrictions on Avandia, a diabetes drug that some say is responsible for tens of thousands of heart attacks and numerous deaths.  

Thirteen members of a 26-member advisory panel convened by the FDA voted to loosen restrictions on Avandia, while seven voted to get rid of the restrictions altogether. Only five voted to keep the current restrictions in place and one member called for an Avandia recall to be issued.

The meeting and subsequent vote came two years after the FDA severely restricted Avandia due to the potential heart side effects, which dropped the GlaxoSmithKline medication from a leading diabetes treatment to a “last resort” drug that is currently only used by about 3,000 patients.

Panel Used Data from Discredited Study

Panel members based their votes on a re-evaluation of a widely discredited clinical trial known as RECORD, which originally indicated that Avandia was free of any significant heart attack risk.

The trial heavily criticized at the time the results were released, as it was unblinded, meaning doctors and GlaxoSmithKline knew which patients were receiving the drug and which were not, and one FDA reviewer, Thomas Marciniak, discovered that the company went in and deleted or changed data to make Avandia appear less likely to cause heart attacks.

Despite the flaws, Duke University researchers “re-adjudicated” the study, looking at the data anew and determined again that there was no Avandia heart attack risk.

The results contradict the findings of some other studies, including a 2007 meta-analysis by Dr. Steven E. Nissen, chairman of the Department of Cardiovascular Medicine at the Cleveland Clinic, which found that Avandia significantly increased the risk of heart attacks.

Before the meeting, Nissen predicted that the FDA would back off of Avandia restrictions in order to save face, suggesting that the panel meeting was only scheduled to try to cover the agency’s own mistakes in failing to act in a timely manner after first learning of information that suggested Avandia could cause heart attacks.

In 2012, GlaxoSmithKline plead guilty to Justice Department charges that it tried to illegally market Avandia and paid fines of about $3 billion. It also paid millions to states for charges that it defrauded their health care programs by failing to provide adequate warning of Avandia heart attacks. The company did not ask the FDA to re-evaluate Avandia, and many experts say it is unlikely that the drug can make a significant comeback even if the restrictions are lifted.

While the recommendations of FDA advisory panels are not binding on the agency, they often weigh heavily in any regulatory decisions. The FDA itself has yet to indicate whether the Avandia restrictions will be eased.

Some reports have suggested that as many as 100,000 heart attacks may have been caused by Avandia, and the drug’s manufacturer has reportedly paid more than $1 billion to settle Avandia heart attack lawsuits brought by former users of the medication who allege inadequate warnings were provided to consumers and the medical community.