For years, scientists have struggled to find a therapy that works for most cystic fibrosis sufferers. Now, two new triple-drug approaches, still undergoing testing, are offering hope.
Cystic fibrosis is caused by mutations in a gene called CFTR. These mutations mean the body either makes defective versions of a protein, also called CFTR, or none of the protein at all. The new therapies work to partly fix underlying problems with one type of defective protein.
Two triple-drug approaches, taken for four weeks, each significantly improved the lung function of people with the most common cystic fibrosis–causing mutation. About 90 percent of people with the disease have this mutation. Plus, the drugs were safe, with tolerable side effects, researchers report online October 18 in two studies in the New England Journal of Medicine.
With continued testing and approval, a triple-drug combination could potentially provide an effective treatment for the first time for the vast majority of cystic fibrosis patients.
The triple-drug approach produced “a really robust improvement in pulmonary function,” says Hartmut Grasemann, a pediatrician at the Hospital for Sick Children in Toronto who was not part of the research. And it “works for almost all patients with cystic fibrosis, which is quite amazing.”
In cystic fibrosis, which affects about 30,000 people in the U.S., the lack of fully functional CFTR protein causes problems throughout the body. Normally, the protein, found in cells lining the lungs’ airways and in other organs, functions as a channel across a cell’s membrane. It regulates the movement of charged particles called chloride ions as well as water into and out of cells.
But when the protein doesn’t work, the lungs become clogged with sticky, thick mucus, which traps invaders like bacteria. As a result, patients have persistent infections which damage the lungs over time, ultimately leading to lung failure. The life expectancy of people with cystic fibrosis varies widely, from below 30 years to around 50 years.
The new triple-drug treatment builds upon the success of an earlier drug, ivacaftor, approved in 2012 for patients who have a rarer mutation that causes the body to make another type of defective CFTR protein. The drug enhanced activity in the protein, increasing lung function and the quality of life for patients, says pulmonologist Steven Rowe of the University of Alabama at Birmingham School of Medicine, a coauthor of one of the new studies. “They are in the hospital much less,” he says, and “the way they feel on a day-to-day basis is substantially improved.”
In the two latest clinical trials, a third drug called a corrector was added to ivacaftor and to another corrector drug called tezacaftor (each trial studied a different version of that third drug). The triple-drug therapies improved lung function compared with those on placebos, the researchers found. On average, all of the patients began the trial with a lung function that’s about 60 percent of what’s normal, based on a breathing test that measures how much air one can forcefully exhale in one second. The lung function of patients taking the therapy increased to about 70 to 74 percent of normal.
“It’s the most exciting thing we’ve seen,” says pulmonologist Jennifer Taylor-Cousar of National Jewish Health in Denver, and a coauthor of one of the studies. If the drugs make it through the final phase of clinical testing, “it will hopefully be life-changing for 90 percent of people with cystic fibrosis.”