UPDATE 2-US FDA sees asthma drug risks, seeks panel advice

Fri Dec 5, 2008 3:01pm EST

(Adds company, analyst comments)

By Lisa Richwine

WASHINGTON Dec 5 (Reuters) - 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," Chowdhury wrote.

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 panel recommendations. (Additional reporting by Susan Heavey, editing by Dave Zimmerman)