The U.S. Food and Drug Administration will ask outside advisers if GlaxoSmithKline Plc's diabetes drug Avandia should be taken off the market or remain on sale with new warnings or limits, a summary released on Thursday said.
The agency has considerable concern about data that shows a signal of possible heart attack risks with Avandia, a summary from FDA staff said. Various data present somewhat inconsistent findings, it added.
The FDA released the summary among more than 400 pages of documents prepared for Monday's advisory panel review of the drug's heart risks.
Glaxo said in documents, also released on Thursday, that its data showed no higher heart attack risk with Avandia than other oral diabetes drugs.
We feel the cardiovascular profile is very reassuring for Avandia, Dr. Anne Phillips, GlaxoSmithKline vice president of clinical development, said in an interview.
Avandia's safety came into question in May when a Cleveland Clinic analysis linked the drug to a 43 percent higher chance of having a heart attack.
That study, by cardiologist Steven Nissen, will not be a focus of the panel meeting, FDA staff said. Agency reviewers said they believe their own analysis used more robust data. Nissen is listed as a non-voting consultant for the meeting.
The panel will be asked if Avandia raises heart attack risk, and if so, how the dangers compare to other diabetes drugs.
If the advisers decide Avandia should stay on the market, the FDA will ask about other steps, such as adding a strong black box warning or limiting use to certain patients.
The FDA usually follows advisory panel recommendations.
Agency staff said combined results from 42 studies showed an increased heart attack risk of about 40 percent, FDA reviewers said, but added that the studies were short with no rigorous follow-up of patients. Longer studies by Glaxo have found no statistical difference between Avandia and some other medicines for combined rates of cardiovascular-related deaths, heart attacks and strokes, they added.
In another memo dated February 2007, FDA staff who monitor drugs already on sale recommended a black box warning about an increased risk of heart attacks and related problems.
The documents said Glaxo in August 2006 had proposed adding language to Avandia's label that included an analysis showing a higher heart attack rate, but with a caveat that the relationship to the drug was not clear.
FDA statisticians also said use of Avandia with insulin should be reassessed, noting a consistent increase in heart attack risk the treatments were combined.
The FDA has already asked for a black box warning about heart failure - a chronic condition in which the heart has trouble pumping blood - on Avandia and rival Actos, made by Takeda Pharmaceutical Co Ltd.
Actos, known generically as pioglitazone, has not been shown to increase the risk of heart attacks or related problems, the FDA's post-approval reviewers said.
The FDA has asked Takeda for a new analysis of heart attack rates with Actos, but the agency documents said it was unlikely results would be ready by the panel meeting.
Glaxo has vigorously defended the drug, known generically as rosiglitazone, but prescriptions have slumped after sales topped $3 billion last year.
Glaxo said Thursday a new company-funded study of health insurance records of more than 400,000 diabetics found heart attack risk was no higher with Avandia than with other oral diabetes drugs. The company said the finding supported previous data.
Summaries from FDA staff and Glaxo were posted on the agency Web site at http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4308b1-00-index.htm.