FDA Scientist Attacks Avandia Safety


Medicare patients in the U.S. who took GlaxoSmithKline PLC's diabetes drug Avandia may have suffered as many as 48,000 heart attacks, strokes and other problems between 1999 and 2009 that could have been averted had they taken a different drug, a Food and Drug Administration scientist contends in a new study.

The unpublished study by outspoken Avandia critic David Graham, an FDA drug-safety official, echoes his earlier assertions and another study led by the Cleveland Clinic's Steven Nissen that linked Avandia to additional heart attacks and strokes.

The FDA is scheduled to review the drug's safety in a meeting next month. Dr. Graham and others have argued that Avandia should be withdrawn from the market. An FDA official said Thursday that Dr. Graham's study would be included in safety data to be reviewed for that mid-July meeting.

Glaxo defends Avandia's safety and opposes withdrawal. Past FDA reviews have allowed the drug to stay on the market because, among other things, it has been shown to lower blood-glucose levels in patients.

The draft study was first published by the Pharmalot blog, which also posted a May 28 email from Dr. Graham to the FDA's senior leaders. In it, Dr. Graham said he wanted to submit the study to the Journal of the American Medical Association for publication. The Pharmalot blog is a respected blog covering the pharmaceutical industry written by Ed Silverman, an editor at large for the industry publication Med Ad News.

In the email, Dr. Graham complained that senior FDA officials were holding up his efforts to publish his work. However, an FDA official, who confirmed the email, said Thursday that the agency isn't suppressing the study and that it was subsequently submitted to the journal.

A JAMA spokeswoman said the journal doesn't ever confirm or deny receipt or acceptance of any manuscript until publication. Dr. Graham couldn't immediately be reached for comment.

FDA officials confirmed the authenticity of the study in which Dr. Graham and colleagues from the FDA and Centers for Medicare and Medicaid Services retrospectively examined the medical records of 227,000 patients 65 and older. The patients took either Avandia, known generically as rosiglitazone, or a competing drug, Actos, also known as pioglitazone, between 2006 and 2009. Many of the patients also took other diabetes drug treatments.

The scientists said that patients taking Avandia had a 27% greater chance of suffering a stroke, a 25% increased risk of suffering heart failure and a 13% greater chance of dying. Avandia increased the overall risk of experiencing heart attack, stroke, heart failure or death by 17%, the study said.

Extrapolating these results to all the people 65 and older who used Avandia from 1999 through 2009, the researchers said they "estimated that about 48,000 elderly patients experienced serious cardiovascular harm or death as a result of using rosiglitazone instead of pioglitazone."

"There is no rationale for [Avandia's] continued availability on the market or its use by prescribing physicians or patients," the researchers conclude.

In an emailed statement, Glaxo said it was "unclear whether this study has been peer-reviewed, and until then, it would be premature to comment." However, the company cited "inherent limitations" with retrospective studies such as Dr. Graham's and said the limitations "can significantly impact the validity of the data."

Glaxo added that results from six clinical trials have shown that Avandia "does not increase the overall risk of heart attack, stroke or death."

A 2007 study by the Cleveland Clinic's Dr. Nissen brought the Avandia safety issues to prominence. He said that Avandia was linked to a 43% greater risk of heart attack.

In February, the Senate Finance Committee revived concern by publishing the results of a two-year investigation that said Glaxo knew about data linking Avandia to higher risk but played down the information and tried to suppress statements by doctors who raised concerns. Glaxo rejected the conclusions and said it only tried to correct misinformation.

Dr. Graham was also a harsh critic of Vioxx, the Merck & Co. painkiller that was withdrawn from the market in 2004.

Avandia was once a multibillion-dollar-a-year medicine and one of Glaxo's top-selling drugs. Since the drug has come under attack, sales have fallen sharply. That has hurt Glaxo and helped competitor Takeda Pharmaceutical Co., maker of Actos.

In the first quarter of this year, world-wide sales of Avandia totaled £169 million ($245.6 million), down 10% from a year earlier.
Write to Jeanne Whalen at jeanne.whalen@wsj.com and Alicia Mundy at alicia.mundy@wsj.com