A Major Milestone in Cystic Fibrosis Treatment

Karen McCoy, MD

Karen McCoy, MD, chief of the Division of Pulmonary Medicine at Nationwide Children’s Hospital

A triple medication combination could be life-changing for the majority of patients with cystic fibrosis.

US News Badge PulmonologyUS News Badge Honor RollA 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 magnitude 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,” says Karen McCoy, MD, chief of the Division of Pulmonary Medicine at Nationwide Children’s Hospital and an author of the study.

“We could tell within hours of starting the medication that something had changed in the patients’ bodies. Patients felt better and had appetites. It transformed the way their bodies worked.”


In a study 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. More than 100 patients with cystic fibrosis ages 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.

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 body mass index.

The findings parallel results from a concurrent phase III trial of the triple therapy in cystic fibrosis patients with a single F508del mutation published in The New England Journal of Medicine.

“This therapy is a major breakthrough that will provide life-changing therapy for nearly all patients with cystic fibrosis. The results that I observed in our patients during the trial, in cases of compassionate use and now after approval are compelling,” Dr. McCoy says, who is also professor of Pediatrics at The Ohio State University College of Medicine. “We will ultimately be able to change the course of this disease dramatically for the vast majority of patients with cystic fibrosis.”

Heijerman HGM, McKone EF, Downey DG, Van Braeckel E, Rowe SM, Tullis E, Mall MA, Welter JJ, Ramsey BW, McKee CM, Marigowda G, Moskowitz SM, Waltz D, Sosnay PR, Simard C, Ahluwalia N, Xuan F, Zhang Y, Taylor-Cousar JL, McCoy KS. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomized, phase 3 trial. Lancet. 2019 Oct 31;394(10212):1940-1948.

A Decade of Remarkable Transformation: Pulmonary Medicine

In the past decade, Pulmonary Medicine has been at the forefront of groundbreaking research and scientific discoveries in cystic fibrosis. Nationwide Children’s serves as a translational research center for the Therapeutics Development Network (TDN) of the Cystic Fibrosis Foundation. As a translational research center for TDN, our patients have access to some of the latest advances in cystic fibrosis treatment.

  • 2010: Keep Me Well Asthma Quality Improvement Initiative Launched
  • 2012: Multiple Regional Outreach Clinics for Pulmonary and Sleep Medicine
  • 2013: Team Performs First Successful Cross-Country Transfer for Pediatric Lung Transplant
  • 2016: Doctors Develop AsthmaCare App Designed for Children and Teens
  • 2018: Cure CF Columbus (C3) Collaboration with Clinicians and Researchers at The Ohio State University Launched
  • 2019: $2 Million Grant Continues Development of Cure CF Columbus (C3) Research and Development Program
  • 2020: Ranked #6 by U.S. News & World Report — Ninth Consecutive Year in Top 10