Vertex Reports Positive Results from Phase 3 Study of Trikafta Children Ages 6-11 Years with Certain CF Mutations

Rare Daily Staff

Vertex Pharmaceuticals reported positive results from a global phase 3 study of its triple combination therapy in children ages 6 through 11 years old with cystic fibrosis, a rare, life-shortening lung disease.

The study was in patients who have either two copies of the F508del mutation or one copy of the F508del mutation and one minimal function mutation. Based on the results, Vertex will submit a supplemental New Drug Application to the U.S. Food and Drug Administration in the fourth quarter of 2020, with additional global regulatory submissions to follow.

“Our aim is to extend eligibility to all patients who may benefit from this transformative medicine, and the positive results from the study in children ages 6 through 11 years old allow us to take another step forward toward this goal,” said Carmen Bozic, executive vice president, Global Medicines Development and Medical Affairs, and chief medical officer at Vertex.

Cystic fibrosis (CF) is a progressive, multi-system disease that affects the lungs, liver, GI tract, sinuses, sweat glands, pancreas and reproductive tract. In CF, certain mutations in the CFTR gene lead to a defective and/or missing CFTR protein. 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 a number of 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 thirties.

Trikafta, a combination of elexacaftor/tezacaftor/ivacaftor, is used for the treatment of cystic fibrosis (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.

The 24-week global phase 3 open-label study evaluated the safety and efficacy of Trikafta in 66 children ages 6 through 11 years old who have either two copies of the F508del mutation or one copy of the F508del mutation and one minimal function mutation. The primary endpoint of the study was safety and tolerability, and the results showed that Trikafta was generally well tolerated and the safety data were consistent with those observed in previous phase 3 studies. In addition, clinically meaningful improvements were seen across multiple secondary efficacy endpoints, including improvements in percent predicted forced expiratory volume in 1 second (ppFEV1), sweat chloride, Cystic Fibrosis Questionnaire Revised (CFQ-R) respiratory domain score, body mass index, and other measures through 24 weeks of treatment. The study showed the benefit-risk profile of Trikafta in children with CF ages 6 through 11 years old was similar to that seen in people with CF ages 12 and older in the phase 3 studies which have supported approval.

Photo: Carmen Bozic, executive vice president, Global Medicines Development and Medical Affairs