A fiery US House of Representatives committee hearing on GlaxoSmithKline's diabetes treatment Avandia has heard that regulators had decided to call for a strengthening of the drug’s label as early as May 23, two days after a meta-analysis called into question the treatment’s safety.
In a written statement to the hearing, the US Food and Drug Administration’s Commissioner Andrew von Eschenbach revealed that the US regulator requested on May 23 "a more prominent warning" for Avandia (rosiglitazone), as well as Takeda and Eli Lilly's Actos (pioglitazone), because "despite existing warnings, these drugs were being prescribed to patients with significant heart failure." Takeda confirmed that it would add a boxed warning, while GSK says it is discussing the request with the FDA.
The hearing is looking at why such a warning had not been applied to Avandia years before when fears of the risk of congestive heart failure surfaced first and the FDA was also criticised for waiting until yesterday to go public with its request, two weeks after the New England Journal of Medicine published the meta-analysis authored by Steven Nissen which suggested that the drug might significantly increase the risk of heart attacks.
Mr von Eschenbach’s letter explained that all the studies "are inconsistent and conclusions are not clear" on Avandia's possible contribution to heart attacks” so that means the FDA “is not at present justified in taking additional regulatory action or recommending that patients stop using it”.
The hearing also heard from GSK’s chairman of R&D, Moncef Slaoui, who said the company "strongly believes that the overall safety of Avandia is comparable to other available oral anti-diabetes medicines". The firm also released yet more new data to support this view, this time from a large-scale observational study of 33,000 patients with type 2 diabetes in a real-world setting and published in Pharmacoepidemiology and Drug Safety.
Expert threatened with lawsuit, called a liar
However there was more to come when endocrinology expert John Buse, who is about to take over as president of the American Diabetes Association, claimed that he was threatened in 1999 by employees of SmithKline Beecham (which later merged with Glaxo Wellcome to form GSK) after he had raised concerns about Avandia.
SmithKline officials allegedly called him a "liar" and challenged his integrity by saying he was "for sale", Dr Buse said, adding that he was then threatened with a lawsuit. "The market capitalisation of the company had declined by $4 billion and there were people in the company who felt I might be liable for that."
After that, Dr Buse sent a letter to Tachi Yamada, then SmithKline's head of R&D, saying: "Please call off the dogs, I cannot remain civilised much longer under this type of heat." He then signed a statement, drafted by the firm, which clarified his views on Avandia and agreed to work with SmithKline to study the drug further. A GSK statement said: "We regret if, at any time, Dr Buse felt the conduct of any GSK employee was contrary to the spirit of open, scientific debate regarding his views on Avandia.”
Away from the hearing, GSK’s chief executive Jean-Pierre Garnier, dismissed comparisons between Avandia and Merck & Co's withdrawn COX-2 inhibitor Vioxx (rofecoxib) in an interview with CNBC. "Vioxx showed the effect in clinical trials. The effect in Avandia was shown in a mathematical analysis, not in a controlled clinical trial. All the clinical trials treating thousands of patients for years have shown no signal," he remarked, adding that there are "four different studies [that] now demonstrate that there [is] no difference between Avandia and the other treatments". He added that “the situation is more complicated in the US because of the political agenda that has been superimposed on the science, and that is unfortunate."