CF treatment may reverse pancreatic damage in young children

In young children with cystic fibrosis (CF), treatment with Alyftrek (vanzacaftor/tezacaftor/deutivacaftor) may reverse a form of pancreatic damage previously thought irreversible.

That’s according to Vertex Pharmaceuticals, Alyftrek’s developer, which presented new data at this year’s North American Cystic Fibrosis Conference (NACFC).

“The data presented at NACFC underscore the safety and efficacy of our CF medicines in the real world and in clinical trials in younger age groups,” Carmen Bozic, MD, executive vice president, global medicines development and medical affairs, and chief medical officer at Vertex, said in a company press release.

Recommended Reading

Sept. 29, 2026 News by Marisa Horak, MS

Next-generation CF treatment found safe for kids as young as 2

Form of pancreatic damage long thought to be irreversible

CF is a genetic disease caused by mutations in the gene that encodes CFTR, a protein that helps regulate mucus production. Lacking functional CFTR, the body produces unusually thick and sticky mucus, which builds up in organs and drives most CF symptoms.

The pancreas is one of the organs most severely impacted by CF. The pancreas is responsible for making enzymes that are needed to digest fats, proteins, and carbohydrates. Normally, these enzymes are made in this organ and then shipped to the intestines — but in CF, thick mucus can block the transportation of enzymes.

This is known as exocrine pancreatic insufficiency, or EPI, and it makes it harder for patients to digest food and absorb enough nutrition. Standard treatment for EPI involves pancreatic enzyme replacement therapy (PERT), where working versions of pancreatic enzymes are released in the small intestine. The vast majority of kids with CF have EPI by the time they turn 1, and it’s long been thought that this pancreatic complication cannot be reversed.

Alyftrek is a triple-combination therapy containing three CFTR modulators, which are medications that can boost the activity of the defective CFTR protein in people with certain mutations. By increasing the CFTR protein’s activity, modulators can help normalize mucus production to ease CF symptoms. Alyftrek was developed as a next-generation successor to Trikafta (elexacaftor/tezacaftor/ivacaftor), an older triple-modulator combination therapy also sold by Vertex.

For decades, pancreatic organ failure and resulting exocrine pancreatic insufficiency has been accepted as an irreversible consequence of CF, but these remarkable data in younger children treated with ALYFTREK show that, in fact, pancreatic failure can be reversed.

Alyftrek is currently approved in the U.S. to treat CF patients with eligible mutations ages 6 and older. Vertex is sponsoring a Phase 3 clinical trial (NCT05844449) testing the therapy in patients as young as 1. The new data cover 48 children ages 2 to 5 who completed approximately one year of follow-up as part of a substudy within that Phase 3 trial. The substudy specifically aimed to assess whether Alyftrek would allow patients with existing EPI to stop needing PERT.

Based on analyses of pancreatic enzyme levels in stool, nearly half (48.6%) of the patients achieved levels above the threshold that typically denotes EPI after about a year on Alyftrek. And more than 1 in 3 patients — 37.5% — were able to discontinue PERT for a mean duration of more than 8 weeks.

The ability to increase pancreatic enzyme levels and allow PERT discontinuation suggests that Alyftrek treatment may actually reverse EPI, according to Vertex. The company noted that, across a total of 66 children in the Phase 3 trial (including those in the substudy alongside additional children in the same age range), 50% did not need PERT as of the latest follow-up.

“The data from the Phase 3 open-label study in 2 to 5 year olds evaluating exocrine pancreatic function represent a profound shift in how we understand the benefits of treating cystic fibrosis in its earliest stages,” Bozic said. “For decades, pancreatic organ failure and resulting exocrine pancreatic insufficiency has been accepted as an irreversible consequence of CF, but these remarkable data in younger children treated with ALYFTREK show that, in fact, pancreatic failure can be reversed.”