Glaxo Stops Study of Asthma Drug
A few important things here. First, this drug was already approved–meaning it was already on the market and this was just a larger follow up study. This study was stopped because it may be associated with an increased risk of life-threatening asthma episodes or asthma-related deaths. HUH?? An asthma drug study is stopped because of side effects of worsening asthma?? Does the word “guinea pig” ring a bell here?
Jan. 24, 2003 — The U.S. Food and Drug Administration (FDA) yesterday announced that an interim analysis of a large safety study of the approved asthma drug salmeterol xinafoate (Serevent 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. At the same time, the drug’s manufacturer, GlaxoSmithKline, 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 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, toward 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, who made up 17% of the study population. 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.”We don’t know why there was this pattern, and would like to do further studies,” Laura Bradbard, a spokesperson for the FDA, told Medscape. “Is it a socioeconomic reason? Is there a problem getting to the doctor often enough? Is the doctor following the guidelines? Or is there a physiological reason why African-Americans have more asthma? It does seem that population suffers from more asthma, and it tends to be more severe. Is it because it’s not being treated, or because it’s being treated too late? There are too many questions. That’s why we need more studies.”The halted 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 the FDA received postmarketing reports of several asthma deaths associated with the use of salmeterol and after publication of studies raising concern about the regular use of short-acting and long-acting beta agonists, including salmeterol. 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 salmeterol 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. 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.The 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 FDA plans to meet with Glaxo soon to obtain more details about the data from the interim analyses of the study and to determine what steps are warranted to address this information, according to a talk paper posted on the FDA’s Web site. The 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.Despite the study stoppage, the FDA emphasizes in the talk paper that based on available data, the benefits of salmeterol for the asthma population continue to outweigh the risks and that the serious adverse events reported in the trial were rare. Patients are strongly advised that they should not stop taking salmeterol, or any other medication, for asthma or COPD, without first talking to their physicians, because abruptly stopping drugs for the treatment of asthma and COPD can result in serious exacerbations of these diseases that could be life-threatening.