Two U.S. drug safety reviewers have recommended that GlaxoSmithKline PLC's diabetes drug Avandia be pulled from the market after concluding it is more dangerous to the heart than a rival medicine, according to documents released on Saturday.
The Food and Drug Administration will again ask an advisory panel to consider the risks of the drug, Glaxo's second biggest-selling product before questions about a possible link to heart attacks emerged in 2007.
Senators Max Baucus and Charles Grassley meanwhile released a report saying evidence suggested Glaxo knew of possible cardiac risks associated with Avandia years before the issue became public.
I await the recommendations of the advisory committee, FDA Commissioner Margaret Hamburg said in a statement.
Meanwhile, I am reviewing the inquiry made by Senators Baucus and Grassley and I am reaching out to ensure that I have a complete understanding and awareness of all of the data and issues involved, she said.
In an October 2008 memo released by the senators, FDA reviewers David Graham and Kate Gelperin concluded the risks of (Avandia) are serious and exceed those for Takeda Pharmaceutical Co's competitor Actos.
They said there was strong evidence that (Avandia) confers an increased risk of heart attack and heart failure when compared to Actos. They estimated that 500 more heart attacks and 300 cases of heart failure were occurring every month with use of Avandia instead of Actos, based on levels of use at the time of their memo.
Graham, an outspoken critic of the FDA's handling of drug risks, had argued to an advisory panel in 2007 that Avandia sales should be stopped. The panel voted 22-1 to urge the FDA to keep the drug on the market.
Glaxo said in a statement the scientific evidence simply does not establish that Avandia increases risks of cardiovascular problems such as heart attacks.
Sales of Avandia, known generically as rosiglitazone, topped $3 billion in 2006 but fell to $1.2 billion in 2009.
The FDA decided in November 2007 Avandia should carry a warning saying a review of 42 studies associated the drug with an increased risk of a heart attack or chest pain compared with a placebo. But it said overall data were inconclusive.
Concerns about Avandia emerged in May 2007 when Cleveland Clinic researchers published a study saying there was a link between the drug and heart attacks.
The senators' report said evidence reviewed by investigators on the Senate Finance Committee, which Baucus chairs, showed Glaxo knew for several years prior to this study that there were possible cardiac risks associated with Avandia.
Glaxo 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 report said.
Committee staff reviewed more than 250,000 documents provided by Glaxo, the FDA and others, the report said. Anonymous whistleblowers provided hundreds of other pages.
The New York Times first reported on the memo from FDA reviewers and the senators' report on Friday night on its website.
Glaxo said it rejected the report's conclusions. The company said the report cherry-picks information from documents, which mischaracterizes GlaxoSmithKline's comprehensive efforts to research Avandia and communicate those findings to regulators, physicians and patients.
Glaxo said it had rigorously studied Avandia's safety and consistently shared this data with regulators around the world. The company said it does not condone any effort to silence scientific debate.
FDA spokeswoman Karen Riley said on Saturday an advisory panel, a group of outside experts, will be asked to provide advice about safety issues with Avandia. The FDA usually follows panel recommendations.
Glaxo spokeswoman Mary Anne Rhyne said the company was told the panel would review results of a Glaxo-sponsored study called Record. That study showed Avandia was not associated with an increase in cardiovascular-related hospitalization or death compared to older diabetes drugs, she said.
The company has asked the FDA for permission to include those results in Avandia's prescribing instructions, she said.
The senators' report was posted at http://finance.senate.gov/sitepages/grassley.htm.
(Editing by Todd Eastham and Vicki Allen)