FDA advisers offer support for GSK asthma drug, not a second
Posted December 11, 2008
Updated December 12, 2008
WASHINGTON — Government health advisers Thursday called for restrictions on some long-acting asthma drugs, but spared GlaxoSmithKline's Advair, a top-selling medication used by millions of patients.
Outside experts advising the Food and Drug Administration recommended that Foradil and Serevent no longer be used for asthma. But they said the benefits of Advair and Symbicort clearly outweigh the risks.Serevent also is made by GSK.
All the medications contain an ingredient that relaxes muscles around stressed airways. But that may mask symptoms that can trigger life-threatening asthma attacks. Advair and Symbicort contain a second ingredient that reduces inflammation inside breathing passages and may help patients avoid such problems.
The FDA's own drug safety experts had recommended restrictions on all four drugs, including that none of them be used to treat asthmatic children. But the agency's respiratory specialists said the risks were manageable and no curbs were needed.
With its own experts deadlocked, the FDA called in an unusually large panel of 27 outside advisers. The medical and scientific experts said Advair and Symbicort should continue to be used with all patients, including children. The vote on Advair was 27-0; on Symbicort it was 26-0. On Foradil nine voted "yes" and 18 said "no," with a "no" vote meaning the risks were greater than the benefits. For Serevent the vote was 10-17.
The FDA usually follows the recommendations of its outside experts.
About 22 million people in the United States suffer from asthma, which claims nearly 3,600 lives. Children account for nearly one out of every three patients. An FDA analysis showed that the risks of long-acting asthma medications, though rare, were greater in children.
The four medications contain a kind of drug called a long-acting beta agonist, or LABA. It relaxes the muscles around stressed airways to help patients breathe.
But medical treatment guidelines say people with asthma should use a LABA together with a steroid to relieve inflammation within the airways. Advair and Symbicort combine both kinds of medicine in one inhaler. But Foradil and Symbicort are LABA-only medications.
In recent years, millions of asthma patients have turned to the long-acting drugs to help them breathe more normally, allowing adults to get nights of uninterrupted sleep, and kids, for instance, to join a soccer team. Advair dominates the market, with almost 4 million patients.
But in rare cases, the drugs can increase the risk of serious asthma complications and send patients to the emergency room gasping for air.
Some experts believe that using a LABA alone can mask developing symptoms, and unexpectedly get patients in trouble. That's why treatment guidelines call for LABA medications to be used with a steroid. Asthma patients also carry a "rescue" inhaler for emergencies.
The companies that make the medications say they are safe, and that at least some of the medical evidence that has raised questions is of poor quality. Doctors who treat asthma had urged the FDA advisers not to ban LABAs.
"If this drug is removed from asthma treatment it would be a disaster," said Dr. Stanley Szefler of National Jewish Health, a Denver health system with a national reputation for respiratory care. He spoke on behalf of the American Academy of Allergy, Asthma and Immunology. Other medical societies voiced similar sentiments.
Baltimore-area teacher Anne Dorsey came to the meeting with her son Julian, 13, who has severe asthma. The mother told the panel that Julian nearly died from an asthma attack in 2006. But he has done much better since then, after he started taking Advair.
"I've spent a lot of time in the hospital," Julian said. "But when I took Advair, life got a whole lot easier."
In preparation for the meeting, the FDA analyzed findings from 110 clinical trials involving nearly 61,000 patients, comparing patients who took a medication containing a LABA with those who used a steroid alone to control their asthma. 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.
Advair, made by GlaxoSmithKline, did not appear to have a higher rate of serious complications when compared with treatment on steroids only. Foradil, Serevent and Symbicort all had higher rates of problems, but the increase was statistically significant only in the case of Serevent.
Serevent is also made by Glaxo. Foradil is made by Novartis and Symbicort by AstraZeneca. That company disputed the FDA's analysis of Symbicort, saying the agency only considered a small slice of available data.