(Adds company, analyst comments)
By Lisa Richwine
WASHINGTON Dec 5 U.S. regulators remain
concerned about serious risks from a class of asthma drugs and
will ask outside advisers if approval for treating the lung
disease should be revoked, documents released on Friday said.
Staff in the Food and Drug Administration's drug-safety
office unanimously have recommended withdrawing clearance of
all long-acting beta agonist drugs (LABAs) for children under
18 amid evidence of an increased risk of asthma-related deaths
and asthma attacks.
LABAs include GlaxoSmithKline Plc's (GSK.L) Advair and
Serevent, AstraZeneca Plc's (AZN.L) Symbicort and Novartis AG's
NOVN.VX Foradil, which Schering-Plough Corp SGP.N markets
in the United States.
The drug-safety staff, which monitors risks of drugs after
approval, also urged removing the approval of Serevent and
Foradil for asthma in people of all ages. Their comments and
findings from other FDA reviewers were released ahead of next
week's advisory panel meeting on LABAs.
Serevent and Foradil contain LABAs only, while Advair and
Symbicort combine LABAs with an inhaled steroid.
Glaxo has argued that adding the steroid may protect
against serious complications. An FDA analysis of several
studies found the risk "was not apparent" in Advair or when a
LABA was used with a steroid, agency documents said.
All of the manufacturers said the benefits of the drugs
outweighed the risks when used as directed.
Advair is Glaxo's best-selling drug.
A memo outlining the advisory panel meeting said the agency
would ask the experts if LABAs should still be approved for
treating asthma. The panel meets Wednesday and Thursday.
Dr. Badrul Chowdhury, director of the FDA division that
reviews pulmonary and allergy drugs, noted a "serious and
significant safety risk" but added the asthma-related deaths
were "numerically small" and the benefits were "not trivial."
"Removal of inhaled LABAs from the market as a treatment
for asthma is a way of managing the risk of these drugs, but
would be an extreme approach that could be problematic,"
The drugs also are approved for treating chronic
obstructive pulmonary disease and would remain available for
treating that lung disease.
Asthma is a chronic disease marked by restricted breathing
and wheezing and often made worse by exercise, cigarette smoke
and other factors. About 20 million people in the United States
have asthma, according to the National Institutes of Health.
LABAs help keep airways open but come with strong warnings
about a higher risk of asthma-related deaths.
The FDA's latest analysis found 2.8 more serious asthma
events for every 1,000 asthma patients treated with a LABA.
Children ages 4 to 11 "appeared to be at the greatest risk,"
FDA statisticians said.
Chowdury questioned the idea that using steroids removes
the risk with LABAs, noting there was no data on that point
from prospectively designed and controlled studies, the type
that provide the strongest kind of evidence.
Deutsche Bank analyst Brian Bourdot said the stance of FDA
reviewers was "no worse than expected" and the consequences for
Glaxo "would appear to be limited" as most use is in adults.
"We doubt the panel would recommend withdrawal of Symbicort
and Advair in adult asthma," Bourdot said in a research note.
A Glaxo statement said the FDA data "confirms the
well-established safety record for Advair." The company said it
was urging a change to Serevent's label to say it should be
used only with an inhaled steroid.
Novartis and Schering-Plough "have confidence in the
efficacy and safety of Foradil," Novartis spokeswoman Maureen
Byrne said via e-mail.
AstraZeneca said its analysis showed no additional risk of
asthma-related deaths or hospitalizations in patients using
products containing formoterol, the LABA in Symbicort.
The FDA will make the final decision but usually follows
(Additional reporting by Susan Heavey, editing by Dave