In the fall of 1999, drug giant SmithKline Beecham secretly began a study to find out if its diabetes medicine, Avandia, was safer for the heart than a competing pill, Actos, made by Takeda.
Avandia's success was crucial to SmithKline, whose labs were otherwise all but barren of new products. But the study's results, completed that same year, were disastrous. Not only was Avandia no better than Actos, but the study also provided clear signs that it was riskier to the heart.
But instead of publishing the results, the company spent the next 11 years trying to cover them up, according to documents recently obtained by The New York Times. The company did not post the results on its website or submit them to federal drug regulators, as is required in most cases by law.
"This was done for the U.S. business, way under the radar," Dr. Martin I. Freed, a SmithKline executive, wrote in an e-mail message dated March 29, 2001, about the study results obtained by The Times. "Per Sr. Mgmt request, these data should not see the light of day to anyone outside of GSK," or Glaxo SmithKline, the corporate successor to SmithKline.
The heart attack risks from Avandia first became public in May 2007, with a study from a cardiologist at the Cleveland Clinic who used data the company was forced by a lawsuit to post on its own website. In the ensuing months, Glaxo SmithKline officials conceded that they had known of the drug's potential heart attack risks since at least 2005.
Early warning
But the latest documents demonstrate that the company had data hinting at Avandia's extensive heart problems almost as soon as the drug was introduced in 1999 and sought intensively to keep those risks from becoming public. In one document, the company sought to quantify the lost sales that would result if Avandia's cardiovascular safety risk "intensifies." The cost: $600 million from 2002 to 2004 alone, the document stated.
Mary Anne Rhyne, aGlaxoSmithKline spokeswoman, said that the company did not provide the results of its Actos study because they "did not contribute any significant new information."
The company said that Avandia is safe and that Freed no longer works for Glaxo SmithKline.
A panel of experts will meet today and Wednesday to decide whether Avandia should still be sold and whether it is ethical to test Avandia directly against Actos.
Whether to withdraw Avandia is a question that has split the FDA, with some officials arguing that the drug is useful despite its risks and others insisting that it must be withdrawn.
According to the documents, Dr. John Jenkins, director of the agency's office of new drugs who has argued internally that Avandia should remain on the market, briefed the company extensively on the agency's internal debate.
"It is clear the office of new drugs is trying to find minimal language that will satisfy the office of drug safety," a top company official wrote in an e-mail message after he spoke with Jenkins, according to a sealed deposition obtained by The Times.
An FDA spokeswoman said the agency would not comment on the contents of the deposition.
Besides the trial comparing Avandia with Actos, the company also conducted trials comparing Avandia with glyburide, a cheaper and older diabetes medicine.
When Rhona A. Berry, a company official, asked about publishing two of the trials, Freed responded in an e-mail message dated July 20, 2001, that referred to Avandia by the abbreviation of its generic name, rosiglitazone: "Rhona - Not a chance. These put Avandia in quite a negative light when folks look at the response of the RSG monotherapy arm," the message said. "It is a difficult story to tell and we would hope that these do not see the light of day."
