(Updated with comments from GlaxoSmithKline starting in the ninth paragraph.)
By Jennifer Corbett Dooren Of DOW JONES NEWSWIRES WASHINGTON -(Dow Jones)- A U.S. Food and Drug Administration panel of medical experts is weighing whether to allow certain drugs to continue to be marketed for the treatment of asthma in children and adults amid lingering concerns that the products increase the risk of asthma-related side effects.
The panel, which includes pediatricians, lung and allergy doctors along with drug-safety experts, is scheduled to vote Thursday whether GlaxoSmithKline PLC's (GSK) Advair and Serevent, Novartis AG's (NVS) and Schering-Plough Corp.'s (SGP) Foradil and AstraZeneca PLC's (AZN) Symbicort should continue to be marketed as asthma treatments. FDA officials have said they are divided about what course of action to take and called on the panel for advice.
The FDA's drug-safety division is recommending that the drugs not be marketed for children, and in some cases adults, while the agency's pulmonary division stated that removing the products from the market would be "extreme."
"We don't have a lot of disagreement in the FDA that the risk is real," said John Jenkins, FDA's office of new drugs director. "Does the risk mean these drugs are unacceptable for marketing?"
The drugs, known as long-acting beta-agonists, or LABAs, are used by about six million asthma patients whose symptoms aren't well-controlled by other drugs including inhaled corticosteroids, which are the backbone of asthma treatment, and are designed to reduce airway inflammation.
Long-acting drugs have been the subject of an on-going FDA safety review for several years and the drugs' labels already warn they could "increase the risk of asthma-related death." The drugs are designed to prevent the tightening of muscles around the airway. About 22 million Americans, including about 6.5 million children, have asthma, a chronic condition marked by narrowing of the airways.
Both the FDA and the companies presented data to the panel Wednesday. The FDA's analysis of the four drugs said, as a group, that the products are linked with an increased risk of asthma-related side effects, with higher risks seen in children. It looked at whether the drugs increased a combined measure of asthma-related death, hospitalization and asthma-related intubations, or the placement of a tube in patients' noses or mouths to help them breathe. Overall, it found an additional 2.8 asthma-events per 1,000 patients treated with a LABA compared to patients not receiving the drugs.
When looking at specific drugs, the FDA said the risk was seen with Foradil, Serevent and Symbicort "but was not apparent in Advair," which is Glaxo's top-selling drug as well as the dominant drug in the class. The agency also said the increased risk was far less when using inhaled corticosteroids, which current asthma-treatment guidelines recommend.
C. Elaine Jones, Glaxo's vice president of respiratory regulatory affairs, said, "it is critical that these medicines remain available to maintain the high standard of asthma care," in a presentation to the panel.
Indeed, the American College and the American Academy of Allergy, Asthma and Immunology along with the American Academy of Pediatrics have said the drugs should remain available as asthma treatments, Jones added. The drugs are used to treat patients with moderate-to-severe asthma.
The FDA said the increased asthma-event rate was largely driven by an increase in hospitalizations. There were 20 asthma-related deaths in the studies; of those, 16 were patients on Serevent and four were patients in the non-LABA group. The analysis involved 110 trials and 60,954 patients. The bulk of the patients were from Serevent trials, with about 43,000 patients, the agency said.
The data were submitted by the four drug manufacturers. The agency also said there was a higher risk of asthma-related side effects among children ages 4 to 11 and among African-Americans but fewer side effects in people age 65 and older.
Glaxo said it would support relabeling Serevent to direct patients and doctors that the product should always be used with an inhaled corticosteroid. Advair, which contains the long-acting ingredient and a corticosteroid, has largely replaced Serevent, which contains only the long-acting ingredient, salmeterol. Both Glaxo drugs are approved for use in children ages 4 and older, as well as adults.
AstraZeneca said Symbicort, which includes a long-acting ingredient along with a corticosteroid, has a "favorable risk-benefit profile." The drug is approved for use in patients ages 12 and older.
Novartis, which makes Foradil, said it found evidence of an increase in non-fatal asthma exacerbations in children ages 5 to 12 but said the data were mostly from a study conducted in the 1990s before treatment guidelines recommended the use of a long-acting drug and a corticosteroid. In the U.S., Foradil is marketed by Schering-Plough. In a statement, the companies said they "have confidence in the safety and efficacy of Foradil."
David Graham, FDA's associate director for science and medicine, said officials in the agency's office of surveillance and epidemiology division think the single-ingredient products, or Serevent and Foradil, should be taken off the market for both children and adults, leaving the products Advair and Symbicort, which also contain a corticosteroid, on the market for adults.
All of the companies have said their products should remain on the market for both children and adults.
-By Jennifer Corbett Dooren, Dow Jones Newswires; 202-862-9294; jennifer.corbett@dowjones.com
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Publié le 10 Décembre 2008 Copyright © 2008 Dowjones