FDA divided on asthma medicines

An FDA scientist argued yesterday that asthma sufferers should no longer use four popular asthma drugs, including GlaxoSmithKline P.L.C.'s Advair and AstraZeneca P.L.C.'s Symbicort, because they may increase the risk of death.

But another scientist from the agency called that opinion "extreme" and said it would leave asthma patients with few treatments.

The comments came during an agency review of drugs known as long-acting beta-agonists, or LABAs. An advisory committee is expected to rule today on whether the drugs should continue to be sold to children and adults with asthma.

FDA scientist David Graham said LABAs had not been adequately studied for safety and effectiveness.

"Basically, we're flying blind," Graham told a committee reviewing the safety of this class of drugs.

Graham was in a minority at the FDA, which last week said Advair was the only LABA that did not increase the risk of asthma complications, including death.

Glaxo said its "comprehensive review of more than 20 years of data demonstrated better overall asthma control with the combination medicine Advair than with a single medicine alone. The data also confirm" its safety record.

U.S. sales of Advair totaled about $4 billion last year, about 96 percent of the market. Glaxo, based in London, has operations in Philadelphia.

The FDA's review also includes Glaxo's Serevent and Novartis AG's Foradil. Glaxo has said Serevent should remain on the market for asthma, but with labeling saying it should be taken only with an inhaled corticosteroid.

AstraZeneca, which has large operations in Wilmington, says its analysis showed no serious risks in patients who took formoterol, the LABA in Symbicort. Novartis and Schering-Plough Corp. also have said Foradil was safe.

A review panel from the FDA safety office is recommending that Foradil and Serevent no longer be used for asthma in any patients and that none of the drugs be used by children 17 and younger.

Badrul Chowdhury, head of the FDA office that oversees respiratory medications, said banning all four drugs for children and adults would be "an extreme approach."

Doctors who treat asthma patients are worried that the drugs could be banned.

"We would be going backward, and the consequences of that would be more untoward effects of asthma," said Paul Greenberger, of Northwestern University, president-elect of the American Academy of Allergy, Asthma & Immunology.

The drugs relax tight muscles around narrowed airways. Medical guidelines for treating moderate to severe asthma recommend use of a LABA together with a steroid, which treats inflammation deep inside the airways.

At yesterday's hearing, however, FDA drug-safety reviewer Andrew Mosholder said evidence that an inhaled steroid nullifies the LABA-related risk was lacking. Foradil and Serevent are LABA-only products. Advair and Symbicort combine a LABA and a steroid in one inhaler.

Some experts say they believe that using a LABA drug alone can mask developing symptoms.

The FDA analyzed findings from 110 clinical trials involving nearly 61,000 patients. Experts looked for deaths, hospitalizations and cases in which a patient had to have a breathing tube inserted. The analysis found 20 deaths from asthma complications, of which 16 were in patients taking a LABA-only drug, Serevent.