Life is short for patients with cystic fibrosis (CF), but not as short as it used to be. In fact, lifetime survival for individuals afflicted with the inherited disease – caused by a single defective gene – has improved drastically since the 1950s when most died during childhood, due to the development of more effective therapies. The future is looking even brighter, according to newly-released results from a Phase 3 combination drug clinical trial, which show that patients with the most common mutation of CF experienced “significant improvements in lung function and other key measures of the disease,” according to a news release from Vertex Pharmaceuticals, which sponsored the trial.

The global randomized, double-blind, placebo-controlled studies, conducted at multiple centers, including the University of Vermont/Fletcher Allen Health Care, included four 24-week combination treatment arms in the studies, known as TRAFFIC and TRANSPORT.

CF, which afflicts roughly 30,000 people in the U.S., causes the production of abnormally thick mucus that blocks airways in the lung and impedes the pancreas’ ability to process enzymes and absorb food. CF patients suffer from frequent lung infections that cause scarring, further limit breathing and require hospitalization. Patients must maintain a strict regimen of breathing and lung-clearing exercises to keep the mucus moving and improve lung capacity.

“We have had multiple patients participate in the Vertex trials leading up to the Phase 3 study,” says Laurie Leclair, M.D., University of Vermont associate professor of medicine and director of the Adult Cystic Fibrosis Center at Fletcher Allen Health Care, which treats about 140 patients from Vermont and upstate New York, including roughly 80 adults and 60 children. “There is tremendous enthusiasm for the most recent trial, because it shows a benefit – improved lung function – for the most common CFTR mutation.”

The two drugs in the current study both target the defective protein underlying CF, which is called cystic fibrosis transmembrane regulator or CFTR. The combination treatment was tested on CF patients age 12 and older with two copies of the F508del mutation. One drug – called ivacaftor and marketed as Kalydeco™ – was used in combination with an experimental therapy called lumacaftor or VX-809.

“Ivacaftor alone targets a mutation only seen in three to five percent of CF patients, but the current study shows that the combination of ivacaftor and lumacaftor is a beneficial, oral therapy targeting the most common underlying defect in CF,” adds Leclair.

In its news release, Vertex states that it “plans to submit a New Drug Application (NDA) by the end of 2014 to the U.S. Food and Drug Administration (FDA) for review, with potential approval in 2015 of the combination treatment for people with two copies of the F508del mutation ages 12 and older.”

PUBLISHED

07-16-2014
Jennifer Nachbur