Rare Daily Staff

The U.S. Food and Drug Administration approved expanded use of Vertex Pharmaceuticals’ Trikafta to include children with cystic fibrosis ages 6 through 11 years with certain mutations.

The expanded approval is for children who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator gene or a mutation in the CFTR gene that is responsive to Trikafta based on in vitro data. The drug was previously approved by the FDA for use in people with cystic fibrosis 12 years and older with at least one copy of the F508del mutation or one copy of a mutation that is responsive in vitro. An additional dosage strength of Trikafta tablets is now available in connection with this approval.

Cystic fibrosis is a rare, progressive, and life-shortening genetic disease affecting approximately 75,000 people worldwide. It is a multi-system disease that affects the lungs, liver, GI tract, sinuses, sweat glands, pancreas, and reproductive tract. CF is caused by a defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene. While there are many different types of CFTR mutations that can cause the disease, most people with CF have at least one F508del mutation. These mutations lead to CF by creating non-working and/or too few CFTR proteins 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 several organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage in many patients that eventually leads to death. The median age of death is in the early 30s.

Trikafta, a combination of elexacaftor/tezacaftor/ivacaftor, is used for the treatment of CF in patients ages 12 years and older who have at least one copy of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Trikafta is designed to increase the quantity and function of the F508del-CFTR protein at the cell surface.

“Today’s approval is a critical milestone in our efforts to deliver medicines that help treat the underlying cause of this devastating disease as early in life as possible,” said Reshma Kewalramani, president and CEO of Vertex. “We can now reach approximately 1,500 newly eligible children in the U.S., and we continue to pursue approval for this expanded indication in other countries.”

Vertex completed a 24-week phase 3 open-label, multicenter study that enrolled 66 children ages 6 through 11 years old with cystic fibrosis who have either two copies of the F508del mutation or one copy of the F508del mutation and one minimal function mutation to evaluate the safety, pharmacokinetics and efficacy of Trikafta. The regimen was generally well tolerated, and safety data were similar with those observed in previous studies of patients ages 12 years and older. The full data from this study were recently published in American Journal of Respiratory and Critical Care Medicine.

Trikafta is already approved for the treatment of patients with CF ages 12 years and older with certain mutations in the United States, Switzerland, Australia, and Israel, as well as in the European Union and the United Kingdom as Kaftrio (ivacaftor/tezacaftor/elexacaftor) in a combination regimen with Kalydeco (ivacaftor). Vertex has submitted applications for use of Trikafta /Kaftrio in children ages 6 through 11 years to the European Medicines Agency and the Medicines and Healthcare products Regulatory Agency (MHRA) and plans to file for this expanded use in Switzerland, Australia and Israel this year.

Photo: Reshma Kewalramani, president and CEO of Vertex

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