Triple Medication Combination Could be Life-changing for Majority of Patients with Cystic Fibrosis

The triple therapy, known as Trikafta, could effectively treat 90% of people with cystic fibrosis.

December 12, 2019

(COLUMBUS, Ohio) – A Phase III clinical trial shows that elexacaftor added to ivacaftor and tezacaftor improves lung function and quality of life in cystic fibrosis patients with the most common genetic mutation, F508del. The triple therapy, known as Trikafta, could effectively treat 90% of people with cystic fibrosis.

“Even though we treated a relatively small number of patients, the size of the effect of this medicine is so huge that it took only small groups to be able to say we have extraordinarily significant results,” said Karen McCoy, MD, chief of Pulmonary Medicine at Nationwide Children’s Hospital and an author of the study.

In a study recently published in The Lancet, Dr. McCoy and her colleagues report the results of a Phase III clinical trial evaluating a next generation CFTR modulator, elexacaftor, in combination with two currently used CFTR modulators, ivacaftor and tezacaftor. The randomized, double-blind trial was completed at 44 sites in four countries. Over 100 patients with cystic fibrosis aged 12 years and older who had two copies of the F508del mutation were randomly assigned to receive the triple therapy or receive ivacaftor plus tezacaftor alone.

“We could tell within hours of starting the medication that something had changed in the patients’ bodies,” said Dr. McCoy, who is also professor of Pediatrics at The Ohio State University College of Medicine. “Within hours, patients felt better and had appetites. It transformed the way their bodies worked.”

Cystic fibrosis is a chronic, genetic disease caused by absence or dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common disease-causing mutation is F508del. Up to 90% of people with cystic fibrosis have at least one copy of this mutation and almost 50% of people with cystic fibrosis are homozygous for F508del.

Over the past decade, CFTR protein modulators have been developed to treat cystic fibrosis. Since CFTR dysfunction caused by F508del is multifactorial, a triple combination of CFTR modulators could result in more improvement.

Treatment with the triple therapy resulted in profound improvements in lung function, sweat chloride concentration and respiratory-related quality of life compared with ivacaftor plus tezacaftor alone, along with a favorable safety profile. Though the trial was only four weeks long, systemic effects were also noted, with rapid improvements in body weight and BMI.

The findings parallel results from a concurrent phase III trial of the triple therapy in cystic fibrosis patients with a single F508 del mutation published in The New England Journal of Medicine.

Dr. McCoy and her colleagues say that this new combination of elexacaftor plus ivacaftor plus tezacaftor is a major breakthrough that will provide effective therapy for nearly all patients with cystic fibrosis and lead to meaningful improvements in their lives. Trikafta was recently approved by the FDA for commercial use. A small group of people with CF have defects that are not improved by modulators, this group remains the focus of intensified research.

“Not only does this triple therapy provide an important clinical benefit on an individual basis, but the number of people that are affected is substantial,” said Dr. McCoy. “We will ultimately be able to change the course of this disease dramatically for the vast majority of patients with cystic fibrosis.”

About Nationwide Children's Hospital

Named to the Top 10 Honor Roll on U.S. News & World Report’s 2019-20 list of “Best Children’s Hospitals,” Nationwide Children’s Hospital is one of America’s largest not-for-profit freestanding pediatric health care systems providing wellness, preventive, diagnostic, treatment and rehabilitative care for infants, children and adolescents, as well as adult patients with congenital disease. Nationwide Children’s has a staff of more than 13,000 providing state-of-the-art pediatric care during more than 1.5 million patient visits annually. As home to the Department of Pediatrics of The Ohio State University College of Medicine, Nationwide Children’s physicians train the next generation of pediatricians and pediatric specialists. The Abigail Wexner Research Institute at Nationwide Children’s Hospital is one of the Top 10 National Institutes of Health-funded freestanding pediatric research facilities. More information is available at NationwideChildrens.org.