Doctor told FDA of Glaxo's Avandia risk in 2000

NEW YORK/LONDON, May 24 (Reuters) A leading doctor voiced concerns about the heart risks of GlaxoSmithKline Plc's diabetes drug Avandia in a letter to the U.S. Food and Drug Administration in 2000, years before Monday's high-profile study questioning its safety.

One year later the FDA criticised the firm for minimising safety concerns, according to documents posted on the agency's Web site that could be used by plaintiff lawyers aiming to sue Glaxo over its second biggest selling drug.

John Buse, president-elect of the American Diabetes Association and faculty member at the University of North Carolina in Chapel Hill, cited ''a worrisome trend in cardiovascular deaths and severe adverse events'' among patients using the drug in a letter to the agency in March 2000 (http://www.fda.gov/ohrms/dockets/dailys/00/apr 00/040500/c01.pdf).

He also accused the drugmaker of ''rampant abuse of clinical trial data''.

The FDA sent Glaxo a warning letter in July 2001 after its own monitoring, saying the company's sales representatives had played down safety concerns and asking the company to send out a letter to doctors warning them of the risks (http://www.fda.gov/cder/warn/2001/10215.pdf).

The company sent out the letters on Sept. 6, 2001, according to the New York Times, which first reported the story.

The news comes after a pooled analysis of dozens of trials, published in the New England Journal of Medicine this week, concluded that Avandia increased the risk of heart attack by 43 percent and cardiac-related death by 64 percent.

Glaxo has disagreed with the study findings. But shares in Europe's biggest drugmaker have fallen 8 percent in the past three days on fears for sales, profits and the risk of lawsuits that could potentially reach billions of dollars.

They slipped again on Thursday and by 0910 GMT were down 0.82 percent at 1333 pence, off a session low of 1328p.

LAWSUITS LOOM A Glaxo spokesman in London, said both the company and the FDA had consistently monitored for adverse events since Avandia's approval in 1999.

''In doing so, the product labelling for Avandia has been updated several times to reflect new data, including with new cardiovascular safety information,'' he added.

''The totality of the data show that Avandia has a comparable cardiovascular profile to other oral anti-diabetic treatments.'' U.S. and European regulators have given a measured response to the new analysis, advising patients to talk to their doctors but not taking any immediate action to restrict Avandia use. The FDA will hold an expert advisory meeting at a later date.

Plaintiff lawyers, however, are expected to latch onto the warnings from years ago as they seek to build a case for bringing product liability lawsuits against Glaxo.

Lawyers said on Wednesday they were already fielding calls from Avandia users, with one predicting lawsuits could run into tens of billions of dollars.

Avandia sales were 1.6 billion pounds ($3.16 billion) and accounted for 7 percent of group revenues -- and significantly more of profits -- in 2006.

Glaxo's chief executive, Jean-Pierre Garnier, told reporters on Wednesday it was too early to say if Avandia would be the subject of lawsuits and he was confident its safety would be vindicated.

He said there had been an ''over-reaction'' to one statistical analysis, which could not be looked at in isolation.

The New York Times reported Buse as saying that his opinion of Avandia had not changed over the years, but that regulators should not rush to judgment and instead await the results of a large study now being conducted by Glaxo.

Industry analysts expect results from the so-called RECORD clinical trial, designed specifically to study cardiovascular outcomes in patients on Avandia, in 2009.

REUTERS SR DB2004