Glaxo SmithKline  Avandia

[but Glaxo telling the truth that MMR in UK is safe?]

Glaxo Knew Avandia Caused Heart Risk, Report Says (Update1)

By Rob Waters

Feb. 20 (Bloomberg) -- Safety reviewers at the U.S. Food and Drug Administration urged the agency to take GlaxoSmithKline Plc’s diabetes drug Avandia off the market in 2008 because they said it was causing 500 additional heart attacks per month. Two U.S. senators say they want to know why the medicine remains on pharmacy shelves.

A report released today by Senators Max Baucus and Charles Grassley said Glaxo knew Avandia may cause heart damage several years before a study documented the risk and the company pressed doctors to retract warnings about side effects. Baucus, chair of the Senate Finance Committee, and Grassley, the committee’s ranking Republican, are pressing the FDA for answers.

Avandia came on the market in 1999 and achieved annual revenue of $3 billion by 2006, including sales of a combination drug that includes Avandia. Sales plummeted to $1.2 billion in 2009, two years after a study was published in the New England Journal of Medicine that linked Avandia to a 43 percent increased risk of heart attack. Two FDA officials also reviewed the drug’s safety and concluded in their 2008 report that Avandia was exposing users to higher risks for heart attacks, or myocardial infarctions, without being any more effective than a rival drug, Tokyo-based Takeda Pharmaceutical Co.’s Actos.

Heart Failure

“These increased risks have caused a substantial excess of acute myocardial infarctions and heart failure that would not have occurred” had Actos been used instead, wrote David Graham and Kate Gelperin, the two FDA officials, in the report. Avandia “should be removed from the market.”

Glaxo, in a statement e-mailed today by Mary Anne Rhyne, a company spokeswoman, said it rejects conclusions that Avandia is risky for patients.

“The scientific evidence simply does not establish that Avandia increases ischemic cardiovascular risk or causes myocardial ischemic events,” she said.

“The FDA considered all the available scientific evidence on Avandia, including Dr. Graham’s assertions of elevated heart attack risk and demands that the product be withdrawn,” the statement said. “Based on the scientific evidence and a recommendation by an independent advisory committee of experts convened by the FDA, the agency has ruled that Avandia remain available to patients for the treatment of Type 2 diabetes.”

FDA Reviewing

Karen Riley, an FDA spokeswoman, said in an e-mail that the agency is “reviewing the report from the senators, we take it very seriously and we will reply quickly.”

In the 2008 report, the FDA safety officers also said that a medical trial comparing Avandia with Actos that was being planned would be “unethical and exploitive” because it would expose patients to unwarranted risks. That trial, called TIDE, which was planned to involve 16,000 patients, is now under way.

Baucus, a Montana Democrat, and Grassley, an Iowa Republican, sent a letter Feb. 18 to FDA Commissioner Margaret Hamburg asking what steps the agency was taking to protect patients in the TIDE trial and demanded a response to their concerns by March 4.

Today’s Senate committee report said executives of London- based Glaxo obtained a copy of the 2007 New England Journal study in advance of its publication from a company consultant who also worked as a reviewer for the journal. Although company scientists internally recognized the study’s validity and acknowledged Avandia’s heart risks, Glaxo prepared a public relations effort to refute suggestions that the drug triggered heart attacks, according to internal e-mails reviewed by Senate researchers cited in the report.

Downplay Findings

“It can be argued that GSK had a duty to warn patients and the FDA of the Company’s concerns,” wrote Baucus and Grassley in the Senate committee report. “Instead, GlaxoSmithKline executives attempted to intimidate independent physicians, focused on strategies to minimize or misrepresent findings that Avandia may increase cardiovascular risk, and sought ways to downplay findings that a competing drug might reduce cardiovascular risk.”

The risks were described in today’s New York Times in a story based on the Senate report and other documents.

Glaxo pressed medical researchers who observed the emergence of heart and liver problems in patients taking Avandia to stop disseminating their findings, contacting the doctors’ superiors in several cases, according to the report.

Glaxo fell 58 cents, or 1.5 percent, to $38.26 in New York Stock Exchange composite trading yesterday. The stock is up 18 percent in the past 12 months.

Sales of Actos, Takeda’s competing drug, were $4.4 billion for the year ended March 2009.

To contact the reporter on this story: Rob Waters in San Francisco at
Last Updated: February 20, 2010 16:36 EST