(From the January 2014 Issue of PediatricsOnline)
Nationwide Children’s Hospital is among the most active clinical trials sites for new cystic fibrosis therapeutics in the country, having enrolled hundreds of patients in close to 80 clinical trials over the past 20 years. These studies not only further the development of important medications for everyone with the disease, but also allow Nationwide Children’s to offer these potentially life-saving treatments to patients in Columbus who may not survive long enough for the drugs to make it to the marketplace.
“We at Nationwide Children’s Hospital are a leading center nationally and have a strong track record of clinical research performance,” says Karen S. McCoy, MD, chief of Pulmonary Medicine at Nationwide Children’s. “Our main motivation for participating in clinical trials such as these is that of the potential benefit these trials offer our patients.”
A member of the Cystic Fibrosis Foundation’s Therapeutic Development Network for more than a decade, Nationwide Children’s is among a small group of selected centers in the United States certified to conduct clinical trials of potential treatments for cystic fibrosis.
About 1 out of every 2,500 Americans has the disease, which is caused by a malfunction in CFTR—a gene responsible for transporting chloride and water across cell membranes. As a result, cells that line the passageways of the lungs, pancreas and other organs produce mucus that is unusually thick and sticky. This mucus clogs the airways, leading to bacterial infections in the lungs, and blocks ducts in the pancreas, reducing insulin production and preventing digestive enzymes from reaching the intestines.
There are about 1,500 mutations in the CFTR that are known to cause cystic fibrosis. Disease severity varies depending on the mutations patients have. When Dr. McCoy first began caring for patients with the disease as a pediatric intern more than 30 years ago, a cystic fibrosis diagnosis was often fatal in childhood.
“Supported by consistent standards of clinical care, effective organization of resources and a nationwide patient data registry, a series of studies have allowed advances in many areas of CF care—brought about by the kinds of clinical trials we’ve conducted here—that have led to significantly improved survival for these patients,” says Dr. McCoy, who is also chief of pediatric pulmonology at The Ohio State University College of Medicine.
One of the recently completed clinical trials at Nationwide Children’s resulted in a gene-specific drug that targets the protein caused by the mutations in the gene G55ID, found in 4 to 5 percent of all patients with cystic fibrosis. The drug, called Kalydeco (ivacaftor), received Food and Drug Administration approval in early 2012.
Another study, currently in phase III trials at Nationwide Children’s, is examining whether combining ivacaftor with another drug currently under study, Lumacaftor, would correct the profound cellular malfunctions caused by the most common genetic mutation in cystic fibrosis, called F508-del, which affects nearly 90 percent of all patients with the disease.
“We have made advances in controlling infection, nutrition, rehydration of mucus secretions and have more exciting potential disease modulators to come. These advances position our patients to live better and longer with a reduced treatment burden,” Dr. McCoy says. “In fact, we are approaching a point where adults with CF outnumber children. We finally have a situation where CF should no longer be a disease which causes fatality in childhood.”