Rare Daily Staff

The U.S. Food and Drug Administration has approved Vertex Pharmaceuticals’ Symdeco (tezacaftor/ivacaftor and ivacaftor) for use in children with cystic fibrosis ages 6 through 11 years with a specific mutation.

The approval covers children who have two copies of the F508del-CFTR mutation or who have at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to Symdeco. The FDA had previously approved it for use in patients with cystic fibrosis 12 years and older with two copies of the F508del mutation or one copy of a responsive mutation.

Cystic gibrosis (CF) is a rare, life-shortening genetic disease caused by a defective or missing cystic fibrosis transmembrane conductance regulator (CFTR) protein resulting from mutations in the CFTR gene. Children must inherit two defective CFTR genes—one from each parent—to have CF. There are approximately 2,000 known mutations in the CFTR gene.

Some of these mutations, which can be determined by a genetic testing, lead to CF by creating non-working or too few CFTR proteins at the cell surface. The defective function or absence of CFTR protein results in poor flow of salt and water into and out of the cell 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, usually in the mid-to-late 20s.

Symdeco is one of several cystic fibrosis treatments discovered by Vertex through its collaboration with CFFT, the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation. Symdeco is also already approved in Canada, Switzerland, Australia, and the European Union for the treatment of CF in patients ages 12 years and older with certain mutations. Vertex plans to submit an application for the use in patients ages 6 through 11 years in the European Medicines Agency in the second half of 2019.

The most recent approval was based on a completed a 24-week phase 3 open-label, multicenter study to evaluate the pharmacokinetics, safety, and tolerability of tezacaftor/ivacaftor and ivacaftor in children ages 6 through 11 years in the United States and Canada. The regimen was generally well tolerated, and safety data were similar to what was observed in previous studies of patients aged 12 years and older. The full data from this study will be published later this year.

“We’ve seen the clinical impact of Symdeco in people with CF aged 12 years and above, and this approval marks a crucial milestone for patients ages 6 through 11 years who may benefit from CFTR modulation, enabling us to treat the basic defect in CF at an earlier stage of disease,” said Seth Walker, University Hospitals of Cleveland, Cleveland Medical Center, Rainbow Babies and Children’s Hospital.

Some mutations result in CFTR protein that is not processed or folded normally within the cell, and that generally does not reach the cell surface. Symdeco is a combination of tezacaftor and ivacaftor (Kalydeco). Tezacaftor is designed to address the trafficking and processing defect of the CFTR protein to enable it to reach the cell surface where ivacaftor can increase the amount of time the protein stays open.

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