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New Therapy Marks A Milestone In Fight Against Cystic Fibrosis

November 4, 2011

Case Western Reserve University School of Medicine, UH Rainbow Babies and Children’s Hospital researcher co-authors major clinical trial

Results of the pivotal Phase 3 clinical trial published in the Nov. 3, 2011 (embargoed 5 pm ET, Nov. 2, ’11) New England Journal of Medicine, find that the oral medication ivacaftor (VX-770) provides major, sustained improvement in lung function, growth and other signs and symptoms for cystic fibrosis (CF) patients. The multi-site study marks the first time a drug has been shown to work on the disease process rather than on the symptoms. CF, which has no cure, is the most common lethal genetic disease in Caucasians.

“Ivacaftor represents a significant advancement in the treatment of CF. This study shows that the therapy can safely provide long-term benefits to patients with a specific type of cystic fibrosis,” said Michael W. Konstan, MD, one of the study’s co-authors 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, a drug developed by Vertex Pharmaceuticals, 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 pivotal Phase 3 clinical trial, conducted in 161 people with CF ages 12 years and older with a specific CF mutation known as G551D (affecting 4 percent of people with CF), showed that taking the oral medication twice daily for 48 weeks improved several key outcome measures of CF, including lung function, growth and sweat chloride levels.

“We have been treating cystic fibrosis for more than 60 years. Current therapies are directed at the complications of the disease,” said Dr. Konstan, who is also Director of the LeRoy W. Matthews Cystic Fibrosis Center at UH Rainbow Babies & 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, MD, PhD, Dean of the School of Medicine and Vice President for Medical Affairs at Case Western Reserve University, wrote, “This success of ivacaftor is a triumph resulting from the discovery of the cystic fibrosis gene in 1989“¦This study is also a great victory in the war against genetic diseases and marks the end of the beginning for the treatment of the cystic fibrosis defect.”

Dr. Davis also wrote that two key questions remain. The first is whether VX-770 can halt deterioration of lung function, which is not clear from this study. The second is if the medication can have an effect on other CFTR defects and possibly benefit more than the 4 percent of patients affected by the G551D mutation. More than 90 percent of CF patients are affected by another mutation called 508-CFTR.

University Hospitals Case Medical Center received funding from Vertex Pharmaceuticals for these studies. Additional support for conducting these and other CF-related studies comes from Case Western Reserve University School of Medicine and Cystic Fibrosis Foundation Therapeutics.

CF affects about 30,000 people in the United States and 70,000 people worldwide. It is caused by a genetic mutation that results in a malfunctioning protein. The resulting imbalance of salt and water causes a cascade of mucus-plugging, infection and inflammation in the lungs. Although other organs also are affected, the primary cause of early death in CF is lung disease. Since the discovery of the CTFR gene in 1989, life expectancy has continued to increase and today is about 37 years.

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