FDA seeks 'black box' warning on Avandia

WASHINGTON -- Two days after a study critical of Avandia was published in the New England Journal of Medicine, regulators asked the drug's maker, GlaxoSmithKline, to add a tougher warning to its prescription labels.

Also today, an FDA employee sent e-mail messages to the media questioning the credibility of Dr. Steven Nissen, the author of the medical journal's report.

Congressional lawmakers are hearing testimony today from regulators, doctors and GSK as it examines whether the Food and Drug Administration and the British drug maker adequately warned patients and their doctors about the possible health risks of Avandia, Avandaryl and Avandamet -- three GSK diabetes drugs containing rosiglitazone. Data published May 21 by the New England Journal of Medicine linked the drug to a 43 percent increased heart-attack risk.

GSK says the study was based on incomplete evidence and inconclusive methods. The company's studies, including one designed specifically to examine heart side effects, have yet to turn up evidence of extra risk.

In written testimony, FDA commissioner Andrew von Eschenbach wrote that on May 23, two days after the journal report, GSK was asked to include a so-called "black box" warning on Avandia's label, to highlight the risks of congestive heart failure. No mention was made of adding a warning about the risks of heart attacks.

Von Eschenbach also testified that a few days after the Nissen study was published, an employee in the FDA's press office sent out e-mail to major news outlets, including the Wall Street Journal, assailing Nissen's credibility and making fun of him. Von Eschenbach said the individual was reprimanded but still has his job.

GSK officials say the drug is safe and an important weapon against diabetes. Avandia generated $3 billion in worldwide sales last year, providing about 7 percent of GSK's total revenue. The company says 6 million Americans have taken Avandia at some point in their lives.

The drug currently carries less explicit warnings about heart failure and cardiac risks and analysts have said stricter warnings could hurt sales.

In other testimony this morning, UNC-Chapel Hill medical school professor John B. Buse told federal lawmakers that GSK pressured him to back off questioning about the safety of the company's diabetes drug Avandia when it came on the market in 1999.

After he raised concerns about the medicine's heart risks, Buse received threatening phone calls from company officials, he wrote in prepared testimony to a House committee. The officials told Buse his actions "were scurrilous enough to attempt to hold me liable" for hurting the company's stock.

Buse's written testimony also said the then-chairman of his department at UNC brought pressure "out of respect for a longstanding academic colleague" who held a senior position with the company. Rather than pursuing his concerns, Buse agreed to work with the drug maker on future studies and signed a statement drafted by the company that was to be used with investors, according to the written testimony.

Buse, soon to become president of the American Diabetes Association, dealt with officials from SmithKline Beecham Plc, which in 2000 merged with GlaxoWellcome Plc to become GlaxoSmithKline. Avandia was developed by SmithKline Beecham.

Congress has been calling for stronger drug safety measures and controls, and the hearing could provide the ammunition to force changes at the FDA.

"Avandia is a case study of the need for reform of our drug safety laws," said Rep. Henry Waxman, a California Democrat and chairman of the House committee, at the start of today's hearing.

GSK shares fell 95 cents in midday trading to $50.95.