Results from two phase 3 clinical trials show that a new combination of medications can successfully treat the underlying cause of cystic fibrosis (CF) for patients 12 and older who have two copies of the F508del gene mutation. This is the most common form of the life-threatening, genetic disease and is found in over half of the cystic fibrosis population. Approximately 8,500 people in the United States, and 22,000 people in North America, Europe and Australia, age 12 and older with cystic fibrosis, carry this gene mutation.

The results of the international trial were published today, May 17,  in the New England Journal of Medicine
 
The trial, which studied more than 1,000 cystic fibrosis patients age 12 and older, revealed that a combination of the drugs Kalydeco (ivafactor) and lumacaftor successfully treated the defective cystic fibrosis protein and improved lung function. The drugs also helped patients achieve a 40 percent reduction in pulmonary exacerbations, the leading cause of death in cystic fibrosis patients. Lumacaftor is an experimental drug that has not yet been approved by the Food and Drug Administration.
 
“Being able to treat not just the symptoms, but also the underlying cause of cystic fibrosis by targeting this specific gene mutation, is a major game changer because it is by far the most common in patients with this disease,” said Dr. Bonnie Ramsey, director of the Center for Clinical and Translational Research at Seattle Children’s Research Institute and professor of pediatrics at the University of Washington. She presented the study’s findings at the Center for Drug Evaluation and Research May 12 advisory committee meeting.

Ramsey noted, “Previously, we found that Kalydeco treated just four percent of cystic fibrosis patients, but this new combination treats the defective CF protein for a much greater number of patients.”
 
The drugs, which work together to address the defective gene mutation by allowing the proteins within the cell to fold properly. reach the cell surface and then work as a salt channel.  The medications were given to patients over the course of 24 weeks in an effort to gain insight on how they may improve lung function and quality of life for people with cystic fibrosis.
 
The trial included cystic fibrosis patients from Seattle Children’s and University of Washington Medical Center. Today, the median predicted age of death for a person with the disease is in the mid-20s.
 
“What gives me tremendous confidence and excites me the most are the comprehensive health improvements seen in patients across all age groups, in all geographies and with all levels of disease severity,” said Ramsey, a pioneer in cystic fibrosis treatment who was one of four lead authors on the trial. “Patients can now have longer periods of good health, greatly improving their quality of life.”
 
The new combination of medications is up for FDA approval in July. If the drug combination is approved, Ramsey and her colleagues will be able to prescribe ivacaftor/lumacaftor to patients age 12 snf older who have the F508del/F508del mutation. There are ongoing safety studies of the drug combination in children 11 years old and younger. These studies are being conducted at sites in the CF Therapeutics Development Network, which is coordinated by Seattle Children’s.
 
“Nothing has been more rewarding than watching the progress of our research over all these years,” Ramsey said. “It has been unbelievable that we began this work 15 years ago with merely a concept of finding a way to treat the underlying cause of this disease, and now, it’s changing patient’s lives. I’m honored to have been able to observe this.”
 
For more information on cystic fibrosis research trials at Seattle Children's, call 206.987.3921.

News Media Contact: Seattle Children’s Public Relations,
press@seattlechildrens.org or 206.987.4500