[e-drug] Study of asthma drug halted

[e-drug@usa.healthnet.org]

E-drug: Study of asthma drug halted
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FDA Press Release January 23, 2003

The Food and Drug Administration (FDA) today announced that an 
interim analysis of a large safety study of the approved asthma drug 
Serevent (salmeterol xinafoate) Inhalation Aerosol suggests that the 
drug may be associated with an increased risk of life-threatening 
asthma episodes or asthma-related deaths, particularly in some 
patients.

The interim analysis did not show a statistically significant result 
for the primary endpoint - a combination of respiratory-related 
deaths or intubations (or ventilatory failure). There was a trend, 
however, towards increases in asthma deaths and serious asthma 
episodes when all patients in the study were considered, though again 
this did not reach statistical significance. A further analysis of 
the data from the study suggested that the risk might be greater in 
African-American patients. Also, further analyses showed that 
patients not taking inhaled corticosteroids at study entry appeared 
to have greater risk for serious outcomes than those who were taking 
inhaled corticosteroids.

This study was designed to further investigate the safety of 
Serevent, particularly whether it might rarely cause serious 
asthma-related adverse events. It was begun in 1996, after FDA 
received post-marketing reports of several asthma deaths associated 
with the use of Serevent Inhalation Aerosol and following publication 
of studies raising concern about the regular use of short-acting and 
long-acting beta agonists, including Serevent. Because asthma 
patients can sometimes suffer sudden, serious life-threatening 
episodes of bronchospasm as a consequence of their disease, the 
deaths and serious adverse events reported for Serevent could neither 
be clearly attributed to use of this product, nor could it be 
excluded as a cause. This study was undertaken to try to help provide 
better information on the safety of this product.

Today, the manufacturer of Serevent Inhalation Aerosol, 
GlaxoSmithKline (GSK), notified investigators that it is stopping 
this study, mostly due to difficulties in enrollment and the 
likelihood the study would not give a clear result, even if fully 
enrolled. The Glaxo Data Safety Monitoring Board overseeing this 
trial conducted the interim data analyses that led to today's action. 
Approximately 26,000 subjects, representing more than 4.3 million 
patient-days of exposure to the drug, had participated in the study. 
The study was intended to enroll 60,000 patients.

FDA routinely monitors adverse event reports as part of its 
continuing efforts to reduce adverse events. Drug safety and risk 
management are among FDA Commissioner Dr. Mark B. McClellan's top 
priorities.

FDA approved Serevent Inhalation Aerosol in 1994 to treat asthma, and 
later this approval was extended to use for treatment of chronic 
obstructive pulmonary disease (COPD). The drug belongs to the class 
of asthma medications known as beta2-receptor agonists (commonly 
called beta agonists). The active drug in Serevent, salmeterol, is 
also contained in the asthma drugs Serevent Diskus and Advair Diskus, 
also manufactured by Glaxo.

FDA plans to meet with Glaxo shortly to obtain more details about the 
data from the interim analyses of the study and to determine what 
steps are warranted to address this important new risk information. 
FDA is particularly interested in further evaluating the question of 
whether certain patients may be at a greater risk for rare, but 
potentially serious adverse events due to Serevent use and use of 
other related drugs.

FDA emphasizes that based on available data, the benefits of Serevent 
for the asthma population continue to outweigh the risks and that the 
serious adverse events reported in the trial were rare. FDA strongly 
advises patients that they should NOT stop taking Serevent, or any 
other medication, for asthma or COPD, without first talking to their 
physicians. Abruptly stopping drugs for the treatment of asthma and 
COPD can result in serious exacerbations of these diseases that could 
be life-threatening. FDA further emphasizes that all asthma drugs, 
including Serevent, should be a given as a part of a comprehensive 
treatment plan that takes into account the patient's asthma severity 
and fully educates the patient in the disease and its proper 
treatment.

An estimated 16 million patients in the U.S. now have asthma, and the 
number of asthmatics has increased significantly in the recent 
decades. In addition to the beta2-receptor family of medications, 
other drugs approved for asthma include leukotriene blockers, inhaled 
corticosteroids and theophylline.


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