(New throughout with disagreement at FDA, company comments)
By Lisa Richwine
ROCKVILLE, Md. Dec 10 U.S. drug reviewers
publicly clashed on Wednesday over how to handle a higher risk
of death and serious complications seen with a class of asthma
medicines now used by millions of patients including children.
The inhaled drugs include one of the world's top-sellers,
GlaxoSmithKline PLC's (GSK.L) Advair, as well as AstraZeneca
PLC's (AZN.L) Symbicort.
Food and Drug Administration staff who monitor drugs after
approval told an advisory panel they felt none of the medicines
known as long-acting beta-agonists (LABAs) should be given to
children with asthma. They also urged revoking approval of two
lesser-used medicines, Glaxo's Serevent and Novartis
AG'sNOVN.VX Foradil, for asthma patients of any age.
"We now know with high certainty that LABAs increase asthma
mortality. Do the health benefits justify that?" asked FDA drug
safety reviewer David Graham, who has been outspoken on
medication risks and criticized the FDA's ability to manage
Graham said the answer clearly was no, as he saw little
improvement among asthma patients treated with LABAs,
particularly children. He estimated that as many as 14,000
deaths could be attributed to LABAs since 1994.
By contrast, the FDA division that reviews asthma drugs
concluded products containing LABAs offered important benefits
with serious risks for a "small" number of patients and should
remain available for asthma treatment with appropriate
warnings, division head Badrul Chowdhury said.
If the FDA decided otherwise, patients might take other
short-acting beta agonists at high doses on a chronic basis,
"This will shift back asthma treatment and asthma care to
where it was about 20 years ago. This shift will not reduce
mortality but may increase it," Chowdhury told the panel.
Chowdhury also said drug-safety reviewers had relied on
data with several limitations.
The FDA will ask the advisory panel to weigh in Thursday.
Glaxo strongly disagreed with Graham's analysis and
defended LABAs as safe and providing benefits of better lung
function, symptom relief and fewer asthma attacks.
AstraZeneca and Novartis said the benefits of their drugs
outweighed the risks when used as directed.
"There is absolutely no clinical scientific evidence that
Advair caused any excess deaths. The public health risk is from
uncontrolled asthma" if proper therapy is not used, Glaxo Chief
Medical Officer Ellen Strahlman said in an interview.
Asthma is a chronic disease marked by restricted breathing
and wheezing and is 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. Uncontrolled asthma can lead to potentially fatal
LABAs help relax airways to prevent spasms but come with
strong warnings about a higher risk of asthma-related deaths in
light of findings from a Glaxo study halted in 2003.
Advair and Symbicort combine a LABA with an inhaled
steroid. Serevent and Foradil, which Schering-Plough Corp
SGP.N markets in the United States, contain LABAs alone.
Advair is Glaxo's best-selling drug with $5.6 billion in
worldwide sales through the first nine months of the year.
Symbicort's sales for the same period were $1.5 billion.
The FDA combed data from 110 clinical trials of about
61,000 people. Reviewers found 2.8 more serious asthma-related
complications, including deaths and hospitalizations, for every
1,000 patients treated with a LABA.
Glaxo argued that adding a steroid to an LABA, as with
Advair, protected against serious risks. Data that raised
concerns came from early studies when it was less common to
pair Serevent with a steroid, the company said.
"Denying access to these life-changing medicines would be
extremely detrimental to patient care," Elaine Jones, a Glaxo
vice president, told the panel.
AstraZeneca and Novartis also said their drugs offered
meaningful benefits and should remain available for asthma
The advisory panel is set to vote on Thursday on whether
the benefits of each drug outweigh the risks for asthma
Approval of the LABAs for asthma could be revoked, but
sales of Advair, Serevent and Foradil could continue for
treating chronic obstructive pulmonary disease (COPD).
AstraZeneca has applied to have Symbicort FDA-approved for
The FDA usually follows panel recommendations.
(Reporting by Lisa Richwine; Editing by Richard Chang; editing
by Carol Bishopric)