Cystic Fibrosis Drug Trial Yields Promising Results

Results of a phase three clinical trial indicated that the candidate drug denufosol, a novel ion-channel regulator, could effectively correct the ion transport defect and resulting mucous build-up that characterize cystic fibrosis (CF).

Cystic fibrosis is an inherited disease that affects the body's ability to move salt and water in and out of cells. This defect causes the lungs and pancreas to secrete thick mucus, blocking passageways and preventing proper function. In addition to causing breathing problems, the mucus becomes a breeding ground for bacteria that can cause serious respiratory infections.

Recently, investigators at the University of Colorado School of Medicine (Denver, USA) published a report summarizing a phase three clinical trial of the drug denufosol, which had been designed to treat cystic fibrosis by correcting the ion transport defect and increasing the overall clearance of mucous by increasing chloride secretion, inhibiting sodium absorption, and increasing ciliary beat frequency in the airway epithelium.

The study comprised 352 cystic fibrosis patients five years of age or older, who received either inhaled denufosol or a placebo three times daily for 24 weeks, followed by a 24-week open-label period when all patients received denufosol. Throughout the study, the patients' exhalation rates and lung volume were measured, and they were monitored for adverse events, such as cough, congestion, fever, or sinusitis.

Results published in the December 17, 2010, online edition of the journal the American Journal of Respiratory and Critical Care Medicine revealed that denufosol was well tolerated with adverse event and growth profiles similar to the placebo. At the end of the 24-week period, the denufosol group showed better lung exhalation rates than those in the placebo group, whose exhalation volumes remained relatively unchanged from the start of the study.

"Abnormal ion transport and defective mucociliary clearance are fundamental defects that contribute to complications of CF lung disease, including mucus plugging, chronic bacterial infection, inflammation, and progressive airway damage,” said first author Dr. Frank J. Accurso, professor of pediatrics at the University of Colorado School of Medicine. "Although currently available drugs target these complications, denufosol was designed to treat the underlying defects that cause the complications, and could potentially modify the course of the disease, particularly when administered early in the disease process."

"Although the lungs of children with CF are thought to be normal at birth, studies have demonstrated significant lung damage that occurs early in life in children suffering from cystic fibrosis,” said Dr. Accurso. "Many patients continue to suffer progressive loss of lung function despite treatment of complications. Because denufosol can be used early in life, it offers hope for delaying or preventing the progressive changes that lead to irreversible airflow obstruction in CF patients.”

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University of Colorado School of Medicine