Cystic fibrosis drug shows promise in trial

By Dr. Ananya Mandal, MDNov 6 2011

The latest clinical trial in its later advanced stags found that oral drug ivacaftor (VX-77) provides major, sustained improvement in lung function, growth and other signs and symptoms for a subset of cystic fibrosis patients.

This came from a multisite study that marks the first time a drug has been shown to work on the disease process rather than on the symptoms, according to researchers. Cystic fibrosis which has no cure, is the most common lethal genetic disease in Caucasians. The study results appear in the Nov. 3 issue of the New England Journal of Medicine.

“Ivacaftor represents a significant advancement in the treatment of CF,” said Michael W. Konstan, a study coauthor and chairman of the Department of Pediatrics at Case Western Reserve University School of Medicine and UH Rainbow Babies and Children's Hospital. “The availability of this medication for these CF patients holds great promise.”

Ivacaftor is developed by Vertex Pharmaceuticals and it targets the underlying cause of CF with the goal of preventing or slowing the development of related complications. Ivacaftor is a “potentiator” of the mutant CF transmembrane conductance regulator (CFTR) protein — the fundamental defect in cystic fibrosis — and acts by restoring the balance of salt and water on the surface of the airways.

The Phase 3 clinical trial included 161 patients of CF ages 12 and older with a specific CF mutation known as G551D (affecting 4% of people with CF). Results showed that those taking the oral medication twice daily for 48 weeks had improved in several key outcome measures of CF, including lung function, growth and sweat chloride levels.

“I've been involved in clinical trials for 30 years,” says the study's lead author Bonnie Ramsey, a professor of pediatrics at the University of Washington School of Medicine in Seattle. “I've never seen this kind of change that has been sustained this long.”

“We have been treating cystic fibrosis for more than 60 years,” said Konstan, who also is director of the LeRoy W. Matthews Cystic Fibrosis Center at UH Rainbow Babies and Children's Hospital. “This drug targets the basic defect of cystic fibrosis. Our hope is that by treating the basic defect, one can prevent complications of the disease, with the ultimate goal of improving the life span of people with CF.”

In an accompanying editorial, Pamela B. Davis, dean of the School of Medicine and vice president for medical affairs at Case Western Reserve University, called the study a “great victory” but wrote that two key questions remain: whether VX-770 can halt deterioration of lung function and whether it can have an effect on other CFTR defects and possibly benefit more than the 4% of patients affected by the G551D mutation. More than 90% of CF patients are affected by another mutation called 508-CFTR.

“This is exciting work,” said Michael Welsh, a pulmonary physician at the University of Iowa who was not involved in the study. “I think that it is very promising for the people who have this particular mutation, and it may turn out to have broader significance.”

“It's creating such a sense of hope and optimism for all the cystic fibrosis patients because this approach will work,” said Robert Beall, president and chief executive of the Bethesda, Md.-based Cystic Fibrosis Foundation, which has spent millions funding such research. The study was partially funded by ivacaftor's maker, Vertex Pharmaceuticals Inc. of Cambridge, Mass., which plans to market it under the name Kalydeco.

If all goes smoothly, ivacaftor may be approved by the Food and Drug Administration in 2012, said study lead author Bonnie Ramsey.