Health regulators said on Monday they would lift restrictions on the use of GlaxoSmithKline Plc's once widely prescribed diabetes drug Avandia, after determining that it did not increase the risk of heart attacks.
The U.S. Food and Drug Administration, following its review of a large clinical trial aimed at determining the drug's heart safety called Record, said it found that the trial showed no elevated risk of heart attack or death in patients being treated with Avandia when compared with standard-of-care diabetes drugs.
These data do not confirm the signal of increased risk of heart attacks that was found in an analysis of previous clinical trials first reported in 2007, the FDA said in a statement.
Avandia, which had been one of Glaxo's top-selling medicines with sales of $3.2 billion in 2006, was pulled from the market in Europe and had severe restrictions placed on its use in the United States in 2010 due in part to ambiguity about a possible increased risk of heart attack and stroke seen in the Record study, as well as a review of other studies.
The drug, known chemically as rosiglitazone, was placed in a highly unfavorable light in 2007 after Dr. Steven Nissen, head of cardiology at the Cleveland Clinic, reported results of a so-called meta-analysis in which data from 42 studies was pooled and analyzed, showing a 43 percent increased risk of heart attack from Avandia.
"GSK welcomes the decision of the FDA and appreciates the agency's robust review of the science with regard to Avandia," Glaxo said in an emailed statement. "GSK maintains its view that Avandia is a safe and effective treatment for Type 2 diabetes when used appropriately."
The British drugmaker had previously said it was not likely to put its marketing muscle behind Avandia again, even if the FDA were to lift usage restrictions. Its U.S. patent protection lapsed in 2011.
"Without patent protection, you probably won't see any marketing spending, or anyone out there promoting Avandia," said Morningstar analyst Damien Conover.
In June, Glaxo said Avandia was being taken by only about 3,000 Americans, down from 120,000 before the restrictions were put in place.
"Our actions today reflect the most current scientific knowledge about the risks and benefits of this drug," Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research, said in a statement.
"Given these new results, our level of concern is considerably reduced; thus, we are requiring the removal of certain prescribing restrictions," Woodcock said.
The FDA decision comes after an independent analysis of the Record study earlier this year appeared to back the safety of Avandia. The FDA had commissioned the Duke Clinical Research Institute three years ago to analyze, or "readjudicate," data from the heart safety trial and report its findings.
"The decision by the FDA is irrelevant in clinical practice," Dr. Robert Tamler, Director of the Mount Sinai Diabetes Center in New York, said by email. "Patients have been reading about increased risk of cardiovascular events with rosiglitazone since 2007 and will not abandon their concerns overnight, despite the FDA decision."
The FDA said it will order changes to the Avandia label to reflect its updated position on cardiovascular safety, will no longer require physicians to register Avandia patients into a Risk Evaluation and Mitigation Strategy (REMS) program, and that diabetes patients will again be able to receive Avandia through regular retail pharmacies and mail order pharmacies.
Glaxo said it would work with the FDA to update the Avandia label and implement FDA decisions on easing of restrictions.
The agency also dropped a requirement that Glaxo conduct a study comparing Avandia to Actos, a diabetes drug from the same class of medicine as Avandia sold by Japanese drugmaker Takeda Pharmaceutical Co.
"It's probably good for the medical community to have the option" to prescribe Avandia, Conover said. "But it will probably be reserved for patients that have failed other drugs, in part because of its checkered past."
(Reporting by Bill Berkrot and Ransdell Pierson; Editing by Gerald E. McCormick, Richard Chang and Leslie Gevirtz)