Rare Daily Staff

The U.S. Food and Drug Administration expanded the approval of Vertex Pharmaceuticals’ cystic fibrosis drug Kalydeco to include use in children with CF ages 12 to less than 24 months with specific genetic mutations causing cystic fibrosis, a rare and life-threatening genetic disease.

CF is 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 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. The median age of death is in the mid-to-late 20s.

“With today’s approval, parents and physicians now have a medicine to treat the underlying cause of CF in patients as young as one year of age,” said Reshma Kewalramani, executive vice president and chief medical officer at Vertex. “We are excited about the progress of our portfolio and continue to support additional research on the potential benefit of early intervention with all of our medicines, with the goal of bringing a treatment to all people living with CF.”

The FDA approval is based on data from the ongoing phase 3 open-label safety study of 25 children with CF aged 12 to less than 24 months who have one of 10 mutations in the CFTR gene. The study demonstrated a safety profile consistent with that observed in previous phase 3 studies of older children and adults. Most adverse events were mild or moderate in severity, and no patient discontinued due to adverse events.

Kalydeco was already approved in the United States for the treatment of CF in patients ages 2 and older who have one of 38 ivacaftor-responsive mutations in the CFTR gene based on clinical and/or in vitro assay data. Vertex submitted a marketing authorization application for a line extension (ages 12 to <24 months) to the European Medicines Agency with a decision expected in the first half of 2019.

August 8, 2018
Photo: Reshma Kewalramani, executive vice president and chief medical officer at Vertex.