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Groundbreaking New Treatment for Cystic Fibrosis



How is a groundbreaking new treatment for cystic fibrosis shifting the standard of care and changing the quality of life for younger patients?

When the U.S. Food and Drug Administration (FDA) approved elexacaftor/tezacaftor/ivacaftor (ETI), a new drug combination designed to treat patients 12 years and older with cystic fibrosis (CF), it was a game changer for this progressive, genetic disease. The pulmonary team at Children’s Hospital Colorado understood the life-changing impact of this drug and played a significant role in clinical trials to prove its safety and efficacy in even younger children. In April of 2023, thanks in part to data from Children’s Colorado, the FDA approved the drug for kids as young as 2 years old — a significant shift and milestone for young children living with cystic fibrosis. But the team doesn’t want to stop there. 

New treatment: cystic fibrosis transmembrane conductance regulator modulator 

This new treatment, called a cystic fibrosis transmembrane conductance regulator (CFTR) modulator, helps restore function to the malfunctioning protein that causes CF. This helps the CFTR protein do a better job of moving chloride ions into and out of the cells and better maintains a balance of salt and water in various organs, including the lungs. This treatment provides remarkable health benefits for up to 90% of people with CF who qualify — those with at least one copy of the F508del mutation.

“We know this drug works by reducing the burden of symptoms,” pediatric pulmonologist Scott Sagel, MD, PhD, says. “It improves lung function, improves growth and reduces pulmonary exacerbations, which are respiratory illnesses that historically led to hospitalizations of people with cystic fibrosis.”

Dr. Sagel worked alongside pediatric pulmonologist Jordana Hoppe, MD, one of the lead investigators in the clinical trial, to help secure approval of this treatment for children as young as 2 years old. They are just two of the many doctors in Children’s Colorado’s Mike McMorris Cystic Fibrosis Research and Care Center, which is one of the largest and most experienced cystic fibrosis clinical care and research centers in the country.

“Before these drugs, our standard of care really was to treat complications of cystic fibrosis,” Edith Zemanick, MD, Associate Director of the Center, says. “We recommended preventative care, like daily mucus clearance, but most of our therapies treated the consequences of CF. The modulators treat the underlying problem, so they get to the cause of all of those consequences.” 

Understanding the new CFTR modulator

While this treatment is a significant breakthrough, doctors at Children’s Colorado and their colleagues across the country are interested in learning how it impacts the whole body for people with cystic fibrosis.

“We don’t know all the things that these protein modulators do for people with cystic fibrosis,” Dr. Sagel says. “It’s a systemic therapy that they take orally and it works throughout the body. How does it change pancreatic function? How does it change liver disease? Does it prevent the progression to diabetes that many people with CF experience?”

Sponsored by the Cystic Fibrosis Foundation, several doctors from Children’s Colorado are helping to lead multicenter studies that are looking at the biology of CFTR modulator therapy. One study, called PROMISE, kicked off first for people with cystic fibrosis 12 and older, looking at the effects of ETI on lung infection and inflammation, CF-related liver disease and glucose homeostasis, among other areas. It is co-led by Dr. Sagel, Children’s Colorado pediatric hepatologist Michael Narkewicz, MD, and pediatric endocrinologist Christine Chan, MD, and taps into two major campus resources: the Center for Biochemical Markers and the Center for Sweat Analysis.

A partner study, called the BEGIN study, is aimed at exploring the same questions in younger age groups. The study began before the drug combination was approved for this younger age range and involves routine testing on blood work and growth parameters. The team wanted to have a deep understanding of what was happening before kids started on modulators to better understand the impacts.

Another part of the BEGIN study involves a bronchoscopy study led by Dr. Zemanick, which aims to help clinicians understand what they can expect for patients when it comes to infections and inflammation in the lungs after starting ETI.

“Our hope is that we won’t need to see kids as often in clinic, and that they may be able to reduce some of their daily treatments, giving them more time to go to school, play and enjoy being a kid,” Dr. Zemanick says. “Kids with CF are at high risk for certain lung infections that we monitor for at clinical visits. Understanding if the chance of infection is lower in kids receiving ETI is going to be really important in informing our care guidelines.”

Psychologists at Children’s Colorado are also exploring the mental health impacts of this new drug combination in partnership with the Cystic Fibrosis Foundation’s National Mental Health Working Group.

Shifting the standard of cystic fibrosis care 

In addition to understanding the impact of ETI on the whole body, doctors are also exploring the shift in the standard of care through a new study, called SIMPLIFY. It asks the question, “What previous typical CF medications can patients stop taking as their symptoms improve with this new drug combination?”

“With cystic fibrosis, we used to do mucus clearance treatments every day, like vest therapy. We would also do mucus-thinning medicines that make it easier to move mucus and cough it out of your lungs. That was the standard of care,” Dr. Sagel explains. The SIMPLIFY study investigated the impact of removing one of those pieces — the mucus-thinning medication. Children’s Colorado was one site in the multisite study collaboration.

The team found there were no significant differences in the group that stopped the mucus-thinning medication, versus the group that continued on the medication. “So, we are now trying to figure out what people with CF do and do not need in terms of their previous standard of care therapies and working to reduce the burden of these treatments if they are unnecessary,” Dr. Sagel says.

Offering hope for the future

“I think the most exciting part is just seeing our patients do so much better,” Dr. Zemanick says. “We’ve always approached CF with a lot of hope, and we expect our kids to do really well. We have many kids who can do all the activities that other kids do, like athletics, but I think this just gives us even more hope for how they’ll do going into adulthood.”

This hope continues to drive the team of doctors at Children’s Colorado who are part of this national effort to improve the lives of children with CF. Their research drives this work forward in impactful ways from all angles.

“Now for many of our children that are starting therapy at a young age, we expect them to have a near normal lifespan,” Dr. Sagel says. “The care model is absolutely going to change. We’re going to go from kids with active disease who we were seeing very frequently, every three months, to kids who are doing well.”

Children’s Colorado is also involved in clinical trials for another drug similar to the recently FDA-approved combination that would be a once-a-day pill instead of twice-a-day. The team is also ready to work on research for future treatments that will help target the 10% of patients who don’t qualify for the currently approved modulators due to their specific mutation and push the age range for existing therapies even lower.

“The goal is to be able to start these medicines shortly after diagnosis,” Dr. Sagel says. “Certainly, from a therapeutic standpoint, this is our best advancement and biggest breakthrough for cystic fibrosis.”