FDA to Re-evaluate Avandia Heart Risks

Avandia Re-Evaluated for Heart Risks by FDA

The U.S. Food and Drug Administration (FDA) will take a second look at a key study defending the safety of Avandia, a former blockbuster diabetes drug the agency tightly restricted in 2010 over heart risk concerns.

The 2009 study, known as the Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Diabetes (RECORD) trial, was sponsored by Avandia’s manufacturer, GlaxoSmithKline.

Although clinical data indicating a more than doubled risk of heart failure prompted European regulators to pull Avandia from the market, RECORD found no increase in cardiovascular-related deaths and helped secure the drug’s availability in the United States. But FDA scientists questioned the validity of the RECORD trial in July 2010, claiming that flaws in its planning and execution make the results on Avandia heart risks inconclusive.

At the request of European regulators, Glaxo funded a re-evaluation of the RECORD trial by Duke University researchers. In a two-part advisory meeting to be held June 5-6, 2013, in Silver Spring, Md., the FDA will discuss the results of the new analysis and determine if further regulations on Avandia are needed.

Avandia Cardiovascular Risks

Avandia, an insulin sensitizer that belongs to the thiazolidinedione (TZD) family of drugs, was released in 1999 to treat patients with type 2 diabetes. Its popularity skyrocketed, and by 2006 the drug had achieved blockbuster status, earning Glaxo $3 billion per year.

But by May 2007, sales started to plummet soon after a New England Journal of Medicine article disclosed that Avandia places patients at a higher risk for heart attack than similar diabetes drugs on the market.

Combining data from 42 clinical trials, the meta-analysis found a 43 percent increase in heart attack risk among type 2 diabetes patients using the drug. Other studies indicated additional risks to heart health, such as a doubled risk of congestive heart failure after one year of treatment with Avandia.

By the end of 2007, Takeda Pharmaceuticals filled the gap Avandia left in the market with Actos, another member of the TZD drug class. Actos eventually became the world’s top-selling diabetes medication, but it too has been linked to severe side effects, including bladder cancer and congestive heart failure.

Avandia’s Restriction, Uncertain Future

As additional evidence of Avandia’s heart risks emerged, regulatory agencies in the United States and Europe took notice.

In a July 2010 FDA advisory committee debate, 20 of the 33 panelists voted to keep the drug on the market, but with a number of serious restrictions. The European Medicines Agency took a stronger stance against Avandia, announcing its intent to halt the marketing and sale of the drug in a September 2010 press release.

As a result of the FDA decision, Glaxo lost the ability to promote Avandia. Patients taking the drug were required to switch to another diabetes medication, and new patients could only get a prescription after signing a release form that states they understand the risks and have no other options for treatment.

At the conclusion of the panel, Glaxo delegated Duke University to perform an independent reanalysis of the RECORD trial. Duke’s findings will be the primary focus of the FDA advisory meeting in June, which may change the availability of Avandia once again.

At this point the outcome of the upcoming advisory meeting is unclear. Glaxo isn’t seeking any new uses for Avandia or trying to expand its use, Glaxo spokeswoman Mary Anne Rhyne told Bloomberg. Regulatory actions could go either way, depending on how the FDA responds to Duke’s reassessment.