By Bill Berkrot and Ransdell Pierson
Nov 25 U.S. 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
"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."