Children’s Hospital Colorado helps prove safety and efficacy of CF treatment in younger pediatric patients

Researchers from Children’s Hospital Colorado Breathing Institute, the largest pediatric cystic fibrosis (CF) clinical care center in the US, participated in the pivotal international multi-center Phase 3 clinical trial sponsored by Vertex Pharmaceuticals Incorporated, which led to FDA approval of TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor), a highly effective treatment for CF, for patients 6 to 11 years of age who have at least one copy of the F508del mutation.

In addition to the TRIKAFTA trial for patients 12 years and older, the team led by Edith Zemanick, MD, a pediatric pulmonologist, principal investigator of the study and associate professor of pediatrics at the University of Colorado School of Medicine on the Anschutz Medical Campus, wanted to prove that TRIKAFTA is safe and effective in even younger patients, as early initiation of treatment is likely to prevent disease progression. The international survey was conducted at 21 locations in five different countries. Children’s Hospital Colorado, in collaboration with the Colorado Clinical and Translational Sciences Institute, enrolled participants who were followed for 24 weeks of treatment. The study led by Zemanick demonstrated the safety and efficacy of TRIKAFTA in children 6 to 11 years of age, consistent with those reported in adults and adolescents, supporting the use of TRIKAFTA in this age group.

When TRIKAFTA was approved in 2019, it became the most effective CF treatment to date, substantially helping about 90% of people with CF. Because of the immediate, robust improvements seen in patients 12 years and older, we wanted to quickly evaluate whether this treatment would be safe and effective for younger patients. Until now, there has been an unmet need to get the most effective treatment for CF for younger children to prevent complications related to CF that are known to start early in childhood.”

Edith Zemanick, MD, Pediatric Pulmonologist

TRIKAFTA, a combination of three molecule therapies, targets the underlying causes of the disease — a defective protein called the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Most people with CF have minimal CFTR protein function. This treatment can significantly improve CFTR protein function, which can reduce many of the symptoms and complications of CF.

In clinical trials, TRIKAFTA treatment led to remarkable improvements in several key measures of disease, including:

Improved lung function by 10% Decreased frequency of pulmonary exacerbations (respiratory diseases requiring hospitalization and antibiotic therapy) Improved weight and body mass index (markers of nutrition) over 24 weeks Decrease in sweat chloride by an average of 61 mmol/L resulting in chloride values ​​below diagnostic level for CF for more than 80% of children. (Sweat chloride test results generally confirm the diagnosis of CF based on a chloride level ≥ 60 mmol/L)

“If we can start TRIKAFTA at an even younger age, the results will be dramatic,” says Zemanick. “Many parents have commented that they did not realize that their child with CF was not feeling well or had as much energy as other children because their lungs were not allowing them to fulfill their potential. Now they can see what their child can do with better lung and nutritional health.”

Zemanick’s team is helping to lead a nationwide CF Foundation-sponsored study called PROMISE and The PROMISE Pediatric Study. Both studies will examine the long-term effects of TRIKAFTA therapy on respiratory tract infection and inflammation, digestive and pancreatic disease, cystic fibrosis-related diabetes and liver disease in the age groups of patients 12 years and older and children 6 to 11 years of age.

In addition to long-term effectiveness studies, Children’s Hospital Colorado is participating in the BEGIN trial to review the effectiveness of TRIKAFTA in infants and children under 6 years of age once medication is available for that age group and the RARE trial to identify treatments for humans with CF who are not eligible for TRIKAFTA based on their underlying genetic mutations.

“Approving TRIKAFTA for younger children is a huge step, but our work won’t be done until we have a cure for CF,” Zemanick said. “We are leading local efforts in the RARE trial to collect cells and biospecimens from the nearly 10% of the cystic fibrosis population with rare mutations. This is to find a highly effective disease-modifying therapy such as TRIKAFTA for the population of patients TRIKAFTA does not work for.”

“I am so proud of the role Children’s Hospital Colorado plays in developing and approving these highly effective treatments for our younger children with CF,” said Scott Sagel, MD, pediatric pulmonologist and director of the University of Colorado Cystic Fibrosis Center. . . “Our successful participation in these clinical trials is a testament to the commitment of our CF research team and children with CF and their families to find better treatments for CF. Children’s Colorado researchers are helping to lead nationwide trials to explore the biology of CFTR to better understand modulator treatment and to determine changes in key biomarkers of lung disease and CFTR recovery.”


Colorado Children’s Hospital

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