FDA advisers weigh asthma drug risks

WASHINGTON - A top FDA scientist said GlaxoSmithKline's drug Advair should be pulled from the market, along with similar drugs that treat asthma.

David Graham, from the Food and Drug Administration's Office of Surveillance and Epidemiology, said this group of drugs had not been adequately studied for safety and effectiveness.

"The risk hasn't been adequately measured for Advair," Graham told a committee reviewing the safety of this class of drugs, during hearings that opened today and will continue tomorrow. "Basically we're flying blind."

His view is a minority at the FDA, which last week issued a report saying Advair was the only drug in this class that did not increase the risk of asthma complications.

The agency's overall report said pulling all the drugs from the market was "an extreme approach that could be problematic" because the drugs relieve symptoms in many patients.

GlaxoSmithKline, in an e-mailed response said: "Our 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 confirms the well-established safety record for Advair."

The widely used asthma inhaler medications - Advair, as well as Serevent, Symbicort and Foradil - already carry strong government warnings. The advisers - about 30 experts representing respiratory, safety and pediatric specialties - will vote tomorrow on whether the risks of the drugs outweigh their benefits for children, teens and adults.

In recent years, millions of asthma patients have started using long-acting drugs to help them breathe more normally, allowing for nights of uninterrupted sleep or workouts at the gym.

But the FDA has been investigating whether the medications, in rare cases, can increase the risk of serious asthma complications, the kinds that send patients to the emergency room gasping for air.

About 22 million people in the United States suffer from asthma, and children account for nearly one out of every three patients. Asthma claims nearly 3,600 lives a year in the U.S.

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 under.

Badrul Chowdhury, head of the FDA office that oversees respiratory medications, says that banning the drugs would be "an extreme approach," and could backfire by leading to more cases of uncontrolled asthma.

The companies that make the medications say they are safe, and that at least some of the medical evidence that has raised questions from the FDA is of poor quality. Doctors who treat asthma patients are worried that the drugs could be banned.

"We would lose a medicine that patients find helpful," said Paul Greenberger of Northwestern University in Chicago, president-elect of the American Academy of Allergy, Asthma & Immunology. "We would be going backward, and the consequences of that would be more untoward effects of asthma. That's a major deal, because asthma hospitalizations continue to be too high."

The four drugs contain a kind of long-acting medication known as a LABA (for "long-acting beta 2-adrenergic agonist"). The drug relaxes 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.

Foradil and Serevent are LABA-only products. Advair and Symbicort combine a LABA and a steroid in one inhaler that patients use every 12 hours. Asthma patients must also carry a "rescue" inhaler to deal with the sudden onset of symptoms.

Some experts believe that using a LABA drug alone can mask developing symptoms, and unexpectedly get patients in trouble. That's why medical guidelines call for LABA medications to be used along with a steroid. But no single theory has won acceptance to explain why some patients have problems.

"The bottom line is we really don't know the mechanism," said Sally Seymour, a safety specialist in the FDA's respiratory drugs office. It doesn't seem that genetic differences are the answer, she added.

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 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, which has a big presence in the Philadelphia region. Symbicort is made by AstraZeneca (which also has a Philadelphia-area presence), and Foradil by Novartis.