FDA Approves Vertex’s Trikafta in Kids 2 to 5 with Cystic Fibrosis

Rare Daily Staff

The U.S. FDA approved the expanded use of Vertex Pharmaceuticals’ Trikafta to include children with cystic fibrosis ages 2 through 5 years who have certain mutations.

The approval is for children with at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or a mutation in the CFTR gene that is responsive to Trikafta based on in vitro data. Trikafta was previously approved by the FDA for use in people with cystic fibrosis 6 years and older with at least one F508del mutation or a mutation in the CFTR gene that is responsive to Trikafta based on in vitro data.

Cystic fibrosis (CF) is a rare, life-shortening genetic disease affecting more than 88,000 people globally. CF is a progressive, multi-organ disease that affects the lungs, liver, pancreas, GI tract, sinuses, sweat glands and reproductive tract. CF is caused by a defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene. Children must inherit two defective CFTR genes — one from each parent — to have CF, and these mutations can be identified by a genetic test.

While there are many different types of CFTR mutations that can cause the disease, the vast majority of people with CF have at least one F508del mutation. CFTR mutations lead to CF by causing CFTR protein to be defective or by leading to a shortage or absence of CFTR protein at the cell surface. The defective function and/or absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus, chronic lung infections and progressive lung damage that eventually leads to death for many patients. The median age of death is in the early 30s.

In people with certain types of mutations in the CFTR gene, the CFTR protein is not processed or folded normally within the cell, and this can prevent the CFTR protein from reaching the cell surface and functioning properly. Trikafta, a combination of three drugs (elexacaftor, tezacaftor, and ivacaftor). It is an oral medicine designed to increase the quantity and function of the CFTR protein at the cell surface. Elexacaftor and tezacaftor work together to increase the amount of mature protein at the cell surface. Ivacaftor, which is known as a CFTR potentiator, is designed to facilitate the ability of CFTR proteins to transport salt and water across the cell membrane. The combined actions of elexacaftor, tezacaftor and ivacaftor help hydrate and clear mucus from the airways.

The label expansion was supported by a 24-week Phase 3 open-label study which enrolled 75 children ages 2 through 5 years old with CF to evaluate the safety, pharmacokinetics and efficacy of Trikafta. The regimen was generally well tolerated, with a safety profile consistent with that observed in older age groups, and led to improvements in sweat chloride concentration, a measure of CFTR function, and lung function. The data from this study were recently published in the American Journal of Respiratory and Critical Care Medicine.

“Early intervention with CFTR modulator therapies like Trikafta can offer the potential to improve the trajectory of CF lung disease,” said Jennifer Goralski, assistant professor of medicine and pediatrics, co-director of the Adult Cystic Fibrosis Center at the University of North Carolina School of Medicine, and a lead principal investigator in the Trikafta 2- to 5-year-old pivotal clinical trial. “With this approval, we now have the ability to treat young children with Trikafta and can proactively address the underlying cause of their disease.”

Photo: Jennifer Goralski, assistant professor of medicine and pediatrics, co-director of the Adult Cystic Fibrosis Center at the University of North Carolina School of Medicine, and a lead principal investigator in the Trikafta 2- to 5-year-old pivotal clinical trial