New hope for cystic fibrosis patients

A combination of two drugs designed to treat the genetic defect present in about half of all cystic fibrosis patients was effective in improving lung function and other symptoms, two new studies have found.

The drugs are ivacaftor — approved in 2012 and sold under the brand name Kalydeco — and the experimental drug lumacaftor. The studies included 1,100 patients ages 12 and older around the world with two copies of the F508del gene mutation — the most common mutation in cystic fibrosis.

Cystic fibrosis is an inherited disease that affects the glands that produce mucus, which keeps the lining of the lungs moist. In CF patients the mucus is thick and sticky, building up in the lungs and airways, and making it hard to breathe.

People with the F508del mutation have a complex form of the disease in which a defective protein that causes cystic fibrosis hides inside the cell. With the two-drug combination, lumacaftor brings the protein to the cell surface, where ivacaftor alters its function and helps fix the normal flow of salt and fluids in and out of the cell.

“This is the first study to show the benefit of using a combination of therapies to correct the functioning of the cystic fibrosis protein and the impact of these therapies on clinical outcomes,” said Dr. Donna Beth Willey-Courand, division chief of pediatric pulmonology at UT Medicine, and director of the Cystic Fibrosis Center at University Health System.

“This study represents a significant step towards the development of therapies that will alter the health and ultimately the survival of patients with cystic fibrosis,” said Dr. Willey-Courand, who wasn’t involved in the research but has prescribed ivacaftor to several of her patients.  “It is incredibly exciting to imagine that one day patients with cystic fibrosis may be offered a gene-specific therapy from the moment of diagnosis. The development of such therapies is truly a game changer in the world of cystic fibrosis care.”

Ivacaftor was approved to treat a different mutation involving a much smaller subset of CF patients. Vertex Pharmaceuticals is expected to seek FDA approval for the combination by the end of the year, based on results of the study.

The Cystic Fibrosis Foundation invested millions in Vertex to spur the research, and the results of the studies were praised in an open letter from Robert Beall, president and CEO of the foundation; and Dr. Preston Campbell, executive vice president for medical affairs of the group.

“These positive results represent an important milestone in the history of CF — and a significant step forward in our effort to bring new treatments targeting the underlying cause of the disease to all people with CF,” Beall and Campbell wrote.

The high cost of ivacaftor, estimated at about $300,000 per patient a year, has generated concerns by some advocates and government officials.

“These results further validate that we are on the right track to finding new treatments targeting the root cause of the disease,” Beall and Campbell wrote. “Even as we celebrate today’s announcement, we are determined to press ahead speedily in our pursuit of new therapies for all people with CF, including those with rare mutations, and we are making steady progress on a number of fronts.”

Photo by Pero, Creative Commons