GlaxoSmithKline Hid Negative Avandia Data: Lawmakers

July 13, 2010— -- WASHINGTON -- GlaxoSmithKline, maker of rosiglitazone (Avandia), hid negative trial results on the controversial diabetes drug more than a decade ago, according to a report released by the Senate Finance Committee.

Rosiglitazone was approved by the U.S. Food and Drug Administration in 1999 to treat type 2 diabetes. But "as far back as 2000, internal e-mails show that GSK executives sought to downplay scientific findings, which raised questions about the safety [of the drug]," the committee wrote, citing an internal memo about a trial comparing rosiglitazone to pioglitazone (Actos) that found rosiglitazone presented a "worse lipid profile" than its competitor.

In another e-mail, sent on July 20, 2001, a GlaxoSmithKline executive, discussing the negative data wrote "we would hope that these do not see the light of day."

Controversy over the drug began three years ago when a 2007 review of data from 42 clinical trials found a 43 percent increase in risk of heart attack among patients treated with rosiglitazone.

Since then, debate has raged over the safety of the drug, and the data have often seemed contradictory at worst and difficult to sort through at best.

The company had projected that if the poor study results went public, GlaxoSmithKline stood to lose $600 million from 2002 to 2004, according to a document obtained by the New York Times.

The paper obtained a sealed deposition that indicated an FDA official -- Dr. John Jenkins, director of the agency's new drugs office -- briefed GlaxoSmithKline on the FDA's internal debate, and told the company his department was "trying to find minimal language that will satisfy the office of drug safety."

In 2007, Congress mandated that drug companies disclose negative trial findings.

According to GlaxoSmithKline spokeswoman Mary Anne Rhyne, the documents reported in the New York Times were obtained from the Senate Finance Committee, which has been investigating rosiglitazone for several years.

GSK Defends Avandia Despite Media Reports

"The documents do not offer new clinically relevant scientific information, and do not provide the full extent of GSK's studies and evaluation of Avandia," Rhyne said in statement.

"[GlaxoSmithKline] has been diligent in providing its safety data on Avandia to the FDA and in publishing its clinical trial data in peer-reviewed journals or on its clinical trial website," she said.

Sens. Max Baucus, D-Mont., and Charles Grassley, R-Iowa -- the chairman and ranking Republican of the Finance Committee, respectively -- said the uncovered documents will help arm the FDA with the best information as it reviews data on rosiglitazone.

"Patients and doctors have a right to know the risks of the medicines they use and prescribe, and drug companies have a responsibility to release data regarding safety concerns about their products," Baucus said in a prepared statement.

Grassley said the handling of rosiglitazone highlights the need to bolster the FDA's post-marketing surveillance of drugs.

"The inequality between the FDA's post-market office and the FDA office that decides whether to approve a drug for market in the first place has led to FDA physicians and scientists who are committed to the post-market monitoring of drugs being suppressed or even ignored, Grassley said in a statement. "A lack of accountability damages public confidence and hope in new drugs. "

A joint advisory panel of outside experts is meeting Tuesday and Wednesday to discuss the future of rosiglitazone. The panel will vote Wednesday on whether to pull the drug from the market. Although several FDA reviewers support yanking the drug, others do not, and the advisory committee will hear conflicting views on the safety and efficacy of the drug over the next two days.

In advance of the hearing, the FDA posted a 765-page briefing document on Friday. In the document, FDA staff reviewers came down hard on rosiglitazone, saying it should be pulled from the market because of serious cardiovascular risks.

Past Avandia Research Under Fire

The document included an analysis of the controversial RECORD trial, which GlaxoSmithKline has leaned on for proof of the cardiovascular safety of rosiglitazone. FDA staff reviewers, led by Dr. Thomas Marciniak, strongly criticized the trial's design, conduct, and results.