Sanders Firm - Wednesday, November 19, 2008 - The Wall Street Journal

Doctors Claim Glaxo Dismissed Worries on Avandia

Drug maker tried to make physicians at Maryland Hospital stop talking about conerns; company defends it's efforts.

A ruckus erupted last year when reports surfaced that Glaxo was accused of intimidating John Buse, a University of North Carolina researcher who, years earlier, questioned the safety of its Avandia diabetes pill, which was linked to heart problems. However, he wasn't the only one the drugmaker tried to stifle.

A doctor from a small Maryland hospital linked Avandia to congestive heart failure in 2000, but Glaxo rejected her warning and tried stop her from talking about it with other docs and hospitals, The Wall Street Journal reports. Glaxo defends its effort, which it says was an attempt to correct "inaccuracies," while the head of the doctor's hospital says he ignored Glaxo's overture.

Mary Money, an internist in Hagerstown, Maryland, tells the paper that she first noticed problems with Avandia shortly after it was launched in mid-1999. But when she and a colleague raised concerns, Glaxo dissmissed them, and the FDA was unresponsive, the doctors tells the Journal.

Last year, the Senate and House began looking at whether Glaxo suppressed info and threatened Buse, charges Glaxo denied. Now the Senate is investigating whether Glaxo's efforts to defend Avandia's safety led to intimidation against other docs who suggested possible links to cardiac dangers. Chuck Grassley, the ranking Republican on the Senate Finance Committee, has demanded documents from Glaxo and is expected to release a detailed report soon, according to staffers.

The backdrop: In May 2007, a study in The New England Journal of Medicine reported that Avandia could raise the risk of heart attack by 43 percent. The FDA subsequently called for a Black Box warning on the Avandia label about the risk of congestive heart failure and heart attack.

Money, meanwhile, had about a patient who came to her in 1999 with congestive heart failure. "That fall, I had a woman patient with massive fluid overload and such shortness of breath that she had to sit up at night," she tells the paper.

The patient had begun taking Avandia two weeks earlier, and an echocardiogram showed high pressure in the arteries of the lungs. Money took the patient off the drug, and within a few days the symptoms almost disappeared. In the next few months, Money and the head of the hospital's diabetes center, Stephen Lippman, found other patients who had similar symtoms, according to the Journal.

Money alerted SmithKline Beecham, the name of the drugmaker before a 2001 merger with Glaxo, which met with her and Dr. Lippman at Washington County Hospital in Hagerstown in April 2000.

The two docs presented data on 85 of their patients who had used Avandia, according to documents from the meeting. More than half of the patients had significant edema, or swelling, and about half of that group also had high pulmonary pressure and shortness of breath. Three had been hospitalized for congestive heart failure. The meeting was a waste of time, Money told the paper. "They came to tell us how wrong we were, not to listen."

Meanwhile, a Glaxo consultant who called into the meeting from the University of Pennsylvania dismissed the Hagerstown doctors' echocardiograms as too poor to show anything useful. "They suggested we were country bumpkins, and practically said, ‘Don't worry your pretty heads. We have smarter people than you looking at this, and there's no problem,'" recalled Lippman, a physician who also holds a doctorate in molecular biology.

A GlaxoSmithKline spokeswoman, Mary Ann Rhyne, tells the Journal that. Money's theories were "unsubstantiated" and she was misinterpreting journal articles to support her case.

The next month, two SmithKline execs wrote to the hospital's chief of staff, calling on him to stop Money from talking about her concerns to other hospital doctors.

"[W]e respectfully ask that your hospital not involve itself in the dissemination of information which has not been substantially verified, and that you take immediate steps to stop the dissemination of this unsubstantiated information to your medical staff," said the letter, signed by two SmithKline executives, which was viewed by the paper.

The Glaxo spokeswoman tells the paper that the letter was justified. "When GSK learns about statements by physicians that are inconsistent with the scientific data on its medicines, it has the responsibility to do what it can to correct these inaccuracies," she says.

The hospital's then chief of staff, Salvatore DiMercurio, decided to ignore the letter after consulting the hospital's executive committee. "It came down to whom do you trust - a doctor you know and have worked with, or the people who are threatening you?" DiMercurio tells the Journal.

Money also contacted the FDA, but she received only a form letter in response. The FDA didn't respond to the Journal for comment. Money and Lippman found themselves at an impasse after Glaxo and the FDA failed to listen to their concerns. Meanwhile, Lippman took a job in California.

Money continued to discourage the use of Avandia when speaking to colleagues, but didn't seek broader attention until last year, when she read about UNC's Buse and Glaxo's reponse when he raised questions about Avandia. In Congressional testimony last year, Buse said he was characterized as a "liar" and threatened with a lawsuit if SmithKline's stock dropped because of his statements about Avandia's possible dangers.

Glaxo upgraded the warnings on Avandia's label more than a dozen times between 1999 and the 2007 including a Black Box. One change, in 2001, said the drug could lead to excessive edema, which in turn could lead to congestive heart failure. But the changes got relatively little notice, and Avandia reached peak world-wide sales in 2006 of $2.5 billion, the Journal writes.

In May 2007, after the New England Journal of Medicine reported the high risk of heart attack linked to the drug, officials in the FDA's safety division recommended the drug be pulled from the market. An outside advisory committee disagreed, but sales since then have plunged. In the first three quarters of this year, Avandia sales were $856.7 million, down 45 percent from a year earlier, according to Glaxo.

The American Diabetes Association and its European counterpart told doctors last month not to use the drug, though it remains on the market.