| June 5
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
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The drug, which was withdrawn from the market in Europe in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 said there was only a "slight" chance that the
meeting will prompt the FDA to greatly ease the sales
"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
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.