June 5 A panel of medical advisers to the U.S. Food and Drug Administration will revive a six-year-old debate over the safety of GlaxoSmithKline Plc's Avandia diabetes drug, but the two-day meeting that starts on Wednesday is not expected to greatly boost sales of the onetime blockbuster product.
Avandia's U.S. patent lapsed in 2011, a year after the FDA heavily restricted its use due to ambiguity about possible increased risk of heart attack and stroke seen in a large trial called RECORD, as well as a review of dozens of other studies.
The drug, which was withdrawn from the market in Europe in 2010 and is taken now by only 3,000 Americans, was once the world's biggest-selling treatment for type 2 diabetes, with sales of $3.2 billion in 2006.
No generic drugmakers have introduced cheaper copycats in the U.S. market and Glaxo has said it has no plans to promote Avandia again, even if the panel of FDA medical advisers recommends lifting restrictions on sales of the drug.
"The FDA is putting significant resources behind this meeting, but even if they allow Avandia to return to full marketing strength, I don't think that would do much for Glaxo from a business standpoint," said Morningstar analyst Damien Conover.
Conover said there was only a "slight" chance that the meeting will prompt the FDA to greatly ease the sales restrictions.
"But if they do, that could signal that the FDA is a little more willing to accept more side effects than it has in the past," Conover said.
Glaxo has settled lawsuits filed by tens of thousands of U.S. patients who had taken Avandia and claimed Glaxo failed to inform them about risks. Several thousand other cases remain pending.
The RECORD safety trial was required by European regulators due to concerns that drugs in its class - called thiazolidinediones - could increase risk of heart failure.
The trial met its primary objective by showing that Avandia, when combined with either metformin or a member of an older class of diabetes pills called sulfonylureas, was at least as safe as the combination of metformin and a sulfonylurea.
But the FDA clamped down on Avandia's use in September 2010 after most members of an FDA advisory panel voted that the RECORD data raised significant concerns that Avandia could indeed pose greater risk of heart attack and stroke than standard treatments, including Takeda Pharmaceutical Co's Actos (pioglitazone), another thiazolidinedione.
Although the FDA allowed Avandia to remain on the U.S. market, the agency commissioned the Duke Clinical Research Institute to analyze results of the RECORD trial to better assess Avandia's safety and to examine criticisms that the trial was poorly designed and its data was mishandled.
But the FDA on Monday, in a briefing document ahead of the two-day meeting this week, said the study's methods and analyses passed muster with the Duke group, part of Duke University's Medical School. Moreover, it said the group appeared to agree that Avandia was not associated in the RECORD trial with increased risk of heart attacks and stroke.
Avandia had been on a downhill slide since 2007, when 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. It showed a 43 percent increased risk of heart attack from Avandia.
Sales of Avandia, which was approved in 1999 and makes patients more sensitive to their own insulin, plunged following the negative publicity, and the FDA now requires heart-safety data for new diabetes drugs because of the Avandia experience.
Glaxo last July agreed to pay $3 billion to settle what U.S. officials called the largest case of healthcare fraud in U.S. history. The agreement resolved allegations that Glaxo failed through 2007 to provide the FDA safety data on Avandia, and that the company improperly marketed other drugs.