Avandia REMS Program Modified by FDA to Loosen Restrictions

In a controversial turnaround, federal drug regulators have agreed to modify the Risk Evaluation and Mitigation Strategy (REMS) program for Avandia, removing restrictions on who can receive the diabetes drug.

The decision comes two and a half years after numerous health experts indicated that the GlaxoSmithKline diabetes drug may have caused tens of thousands of heart attacks and recommended restrictions that have virtually ended all prescriptions for the medication.  

On November 25, the FDA announced that it is removing some Avandia prescribing and dispensing restrictions; primarily those involving the Avandia REMS Program.

The decision was anticipated after an FDA advisory committee met over the summer to discuss the Avandia restrictions, determining that the agency was wrong to restrict the drug and that data indicates that there may be no significantly increased risk of heart attacks with Avandia. However, the advisory panel has been sharply criticized by many, including the doctor who first raised the alarm bell about Avandia. Critics have suggested that the agency is trying to save face after it failed to initially protect the public from the potential side effects of Avandia.

“Our actions today reflect the most current scientific knowledge about the risks and benefits of this drug,” Janet Woodcock, M.D., director of the FDA Center for Drug Evaluation and Research said in a press release. “Given these new results, our level of concern is considerably reduced, thus we are requiring the removal of certain prescribing restrictions.”

The changes to the Avandia REMS program includes removal of restrictions limiting the drug to certain patients and the removal of certain warning label information. Health care professionals will also no longer be required to enroll in the Avandia REMS program before prescribing the drug, essentially eliminating the program altogether.

However, the FDA is leaving in place requirements that GlaxoSmithKline and generic Avandia manufacturers provide training to health care providers on the potential heart risks of Avandia, noting that there is still some “scientific uncertainty” regarding the drug’s risks.

The move was long predicted by Dr. Steven E. Nissen, who warned of Avandia heart problems in a 2007 meta-analysis. Nissen, chairman of the Department of Cardiovascular Medicine at the Cleveland Clinic, said earlier this year that the FDA would drop restrictions on the drug to save face, knowing that there was almost no way an Avandia come back was possible at this point.

The FDA initiated a review of the drug without any request from GlaxoSmithKline that the agency do so.

Drug Trials Questioned

The decision was based off of 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 was 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. In addition, 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 and that the Avandia REMS program was unnecessary.

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.

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.