Recent reports point to GlaxoSmithKline long being aware of Avandia’s cardiac risks. In 2007, a Cleveland Clinic study conducted by prominent cardiologist Dr. Steven Nissen and published in the New England Journal of Medicine (NEJM) found that patients taking the diabetes drug experienced a 43-percent higher risk of suffering a heart attack. Many called for Avandia’s recall, but as Wall Street Journal (WSJ) reports today, Glaxo argued against the findings. Now, some details of Glaxo’s behind-the-scenes Avandia cover-ups are being made public.
Glaxo emails prove its own researchers were worried its findings mirrored Nissen’s study says the WSJ. Following release of the study, both Glaxo and the U.S. Food & Drug Administration (FDA) came under fire for a failure to warn the public about Avandia’s risks. Also, 2007 Congressional testimony revealed both groups knew about the cardiac risks in 2005 and an FDA scientist who advocated for a strong black box warning alleged that the damaging information was removed from an Avandia safety review. Just before the study was published, reports WSJ, Glaxo’s senior consultant wrote in an email, “The numbers are the numbers, the analysis is very similar to our own.”
Despite overwhelming evidence to the contrary, Glaxo and the FDA continue to defend Avandia. Janet Woodcock, FDA drug review division director, recently said that Avandia was “convicted without a trial,” quoted the WSJ. Glaxo also maintains it did not hide that it conducted its own meta-analysis and found similar cardiac results as the study and that it provided the information to the FDA.
Meanwhile Senator Chuck Grassley—Repubican-Iowa—has been after the FDA to have Glaxo withdraw Avandia and is working on a report expected to contain information from Glaxo’s own documents on its efforts to defend Avandia, said the WSJ, which noted that about 1,000 patients have filed suit against Glaxo. The WSJ reported that the study was to be kept secret until its late-May 2007 release; however, Glaxo got hold of it in advance from University of Texas Dr. Steven Haffner, a Glaxo Avandia consultant since 2000, who reviewed the piece for the NEJM. Haffner acknowledged he gave Glaxo the study in advance and said his action was “a terrible mistake.”
Dr. Nissen told the WSJ that he was visited by some top members of Glaxo’s scientific team, including its chief medical officer, just prior to the piece’s publication and was asked to rethink his conclusions. Said Nissen, “They never revealed that they had obtained a copy of our manuscript and had concluded that our findings were irrefutable. Instead, they attacked the validity of the study and the motives of both the authors and the NEJM.”
The WSJ also released a number of damaging email excerpts. For instance, one email stated that, “There is no statistical reason for disregarding the [Nissen] findings as presented” and Moncef Slaoui’s, director of Glaxo research, said: “FDA, Nissen and GSK all come to comparable conclusions regarding increased risk for ischemic events, ranging from 30% to 43%!”
Defending itself from Nissen’s conclusion, WSJ reported that Glaxo released interim results of a study called “Record”; however some at Glaxo were concerned this would fail and one scientist’s email states, “What’s to stop [Nissen] adding the events from Record to his meta-analysis and re-enforcing his view?” The NEJM, after receiving the Record results from Glaxo responded with: “The editors feel strongly that your data do not support the statement that the Record results for MI [myocardial infarction or heart attack] contradict the Nissen meta-analysis…. This statement must be removed or modified,” quoted the WSJ. So, Glaxo responded with a revision that said the drug might be linked to higher cardiac risks but did not increase the risk of heart attack or death, said WSJ. The NEJM included an editorial by Massachusetts General Hospital endocrinologist David Nathan, which said the study “fails to provide exculpatory evidence” about Avandia, noting that too many participants left the drug trial.
The FDA is also facing some heat. At a June 2007 Congressional hearing, FDA commissioner, Andrew von Eschenbach, defended the FDA’s refusal to remove Avandia from the market or significantly strengthen its warning saying that the agency’s own analysis was in progress, reported the WSJ. In a clear contradiction, a press release issued by the agency claimed it had only recently received information from Glaxo about its 2005 meta-analayis; however, the FDA received that data a year before the NEJM according to Glaxo emails and a Glaxo statement this week, the WSJ said.
The WSJ reports that the FDA declined to comment and Glaxo refused to make employees connected with the damaging emails available to it for comment.