FDA expected to weigh in on Avandia risk

With the future of GlaxoSmithKline's Avandia diabetes drug hanging in the balance, the Food and Drug Administration was expected to release a key staff report on suspected health risks Friday that likely will figure prominently in deciding whether the drug should remain on the market.

Two studies released last week concluded patients taking Avandia faced an elevated risk of heart attacks and strokes, and the drug has long had critics demanding that it be withdrawn from the market.

But other research has found no health risk at all, and the company has asserted that the drug is safe.

"There is a broader context here because there are a number of very vocal critics of the drug," said Les Funtleyder, portfolio manager and health-care strategist at the investment firm of Miller Tabak. "There have been a number of drug recalls, so the FDA is likely to be quite cautious."

The FDA staff report and related documents will be made public as part of the agency's reconsideration of the drug's safety and efficacy.

While important, the agency's findings are intended mainly to serve as guideposts for a panel of outside scientific experts who will meet just outside Washington for two days next week to evaluate evidence suggesting that patients taking Avandia have a higher risk for heart attack, strokes, and congestive heart failure.

Typically, such advisory committees vote on whether a drug should remain on the market, sometimes with a new or revised warning label, or be withdrawn.

Most often, the FDA follows the committee's recommendation.

But it can be difficult to predict the outcome. In 2005, after congressional hearings and searing public criticism of Merck & Co. for marketing Vioxx as clinical data emerged that patients taking the painkiller were at increased risk of heart attacks and strokes, an FDA advisory committee voted to allow the drug to remain on the market.

A majority of the panel said clinical data pointing toward risk was outweighed by evidence that Vioxx was the only effective painkiller for some patients, and that the risk could be managed. The company, which had earlier withdrawn the drug from the market, did not reintroduce Vioxx, despite the finding.

"I think it is going to be put in the hands of the advisory committee, and I think that it is going to be a coin toss," said Tim Anderson, global pharmaceutical analyst at Sanford C. Bernstein & Co., the investment firm.

London-based GSK is a global pharmaceutical giant with major operations in the Philadelphia area. It employs about 5,000 people in Center City and in two large research facilities in Upper Providence and Upper Merion.

"Since 2007, we have seen results from six controlled clinical trials looking at the cardiovascular safety of Avandia, and together they show that this medicine does not increase the overall risk of heart attack, stroke or death," said Murray Stewart, vice president for clinical development at GSK. "We also know that Avandia lowers glucose levels in both the short- and long-term and is the only oral antidiabetic medicine that has been shown to sustain blood-sugar control for up to five years."

Sales of Avandia last year were about $800 million worldwide, but Anderson, of Sanford Bernstein, said that sales had been trending downward. If the drug were withdrawn from the market, it likely would not have a material impact on GSK, which had total sales of $28 billion last year, he said.

Avandia was approved by the FDA to treat Type 2 diabetes, which typically is linked to obesity. One other drug, Actos, made by Takeda Pharmaceutical Co. of Japan, has been approved by the FDA for the same purpose, but it has not been associated with any health risks, leading critics to question why Avandia should remain on the market.

One of the studies released last week, a review of 227,000 Medicare patients, found that taking the drug increased the risk of heart attack and stroke by 17 percent.

The other, by Cleveland Clinic cardiologist Steven Nissen, an analysis of clinical trials involving 35,000 people, reported that patients using Avandia had an increased risk of heart attack of as much as 39 percent.