Avandia: the FDA is on the defensive now

In an obvious attempt to save face, the U.S. Food and Drug Administration (FDA) yesterday announced severely toughened black box warnings for Avandia, and Actos – two diabetes drugs strongly suspected of increasing the risk of heart attack.

In front of a packed Congressional hearing yesterday called to investigate the long delays by regulators in addressing the Avandia safety concerns, FDA Commissioner Andrew C. von Eschenbach released a written statement that shows the FDA has formally asked GlaxoSmithKline, the makers of Avandia – as well as Takeda Pharmaceuticals and Eli Lilly and Company, the makers of rival diabetes drug Actos – to put black box warnings on their product packaging. The matter was raised with the respective drug manufacturers on May 23rd of this year, two days after long-held Avandia safety concerns hit the media.

The irony, here, is that the FDA chose a hearing into its own conduct to announce a safety upgrade. What’s even more ironic is long before recent findings in the New England Journal of Medicine (NEJM) stirred the pot and put Avandia on the front pages, the FDA’s own safety reviewers strongly recommended exactly what the FDA finally got around to doing yesterday.

It took them over a year to act.

Little wonder that there appears just as much anger directed at the FDA, as there is towards drug manufacturers for putting out products that could potentially harm millions of unsuspecting Americans.

At the same hearing yesterday, Dr. John B. Buse, Chief of Endocrinology at the University of North Carolina medical school and incoming president of the American Diabetes Association, testified that when he first raised concerns about Avandia as far back as 1999 – the year it was approved – manufacturer SmithKline Beecham came down on him hard.

During a presentation to the American Diabetes Association in 1999, mere months after Avandia had been approved by the FDA, Dr. Buse outlined his concerns over data that suggested taking Avandia would raise the risk of heart attack and chest pain by 50 percent.

“In the week that ensued,” Dr. Buse went on in his prepared statement, “there were a number of phone calls from SmithKline Beecham (forerunner to GlaxoSmithKline). During these calls, it was mentioned on two occasions that there were some in the company who felt my actions were scurrilous enough to attempt to hold me liable for a loss in market capitalization.” The reference was to a decline in the company’s stock price representing a loss of U.S. $4 Billion. Essentially, Buse was threatened with the possibility of seeing himself held personally liable for the loss, in addition to being called a scoundrel and a liar, and accused of selling out, simply for speaking up.

The executive who is alleged to have made the threats is now working for the Bill and Melinda Gates Foundation.

The continuing drama in Washington saw Representative Henry A. Waxman, the chair of yesterday’s panel of the House Committee on Oversight and Government reform and a California Democrat, taking the FDA to task, accusing the regulator of “dropping the ball” on the Avandia safety portfolio. Asked whether the FDA needs more Congressional authority, Dr. von Eschenbach replied that the organization needs more money.

One wonders, however, if more money would have avoided the reprimand handed to Dr. Rosemary Johann-Liang, a drug safety supervisor for the FDA. In an interview, Dr. Johann-Liang revealed that she advocated the very same black-box warning announced by the FDA June 6.

That was in March 2006. Over a year ago.

And in a telling state of affairs, Representative Stephen F. Lynch from Massachusetts asked the three FDA witnesses to look at the current Avandia packaging in an effort to find where it referred to the potential for heart attacks.

Dr. von Eschenbach deferred the sleuthing to his colleague, Dr. John K. Jenkins, who also appeared before the panel along with the FDA’s Dr. Gerald J. Dal Pan.

“Have you found it yet?” Rep. Lynch kept hounding, while Jenkins kept looking, and all three – obviously not expecting the question – appeared confused.

Jenkins finally found the reference to heart attack risk in a small table, contained in the labelling information.

“That’s it?” Rep. Lynch asked.

“You’re not seriously telling me, that that’s it?”

In response to the current controversy over Avandia and in an attempt to save its market share, GlaxoSmithKline has undertaken a more thorough study, and released preliminary results June 4th, two days before the expected raucous proceedings in the House review. GlaxoSmithKline, in publishing its findings in the New England Journal of Medicine on Monday, had hoped that more favourable conclusions would aid a multimedia news blitz defending the drug.

Instead, many of the doctors who analyzed Glaxo’s findings concluded that there remains a very real concern with Avandia, a product used by millions around the world.

Avandia has been a solid performer for GlaxoSmithKline, with annual revenues exceeding U.S. $3.2 Billion.

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