FDA Approves Ivacaftor for Cystic Fibrosis in Certain Children with Mutations in CFTR Gene


The FDA has approved ivacaftor (KALYDECO) as the first and only medicine to treat the underlying cause of cystic fibrosis in children ages 12 to

The US Food and Drug Administration (FDA) has approved ivacaftor (KALYDECO) to include use in children with cystic fibrosis ages 12 to <24 months who have at least 1 mutation in their cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to the drug.

“Cystic fibrosis is a chronic, progressive disease that is present at birth, with symptoms often occurring in infancy,” said Reshma Kewalramani, MD, executive vice president and chief medical officer at Vertex, in a recent statement. “With today’s approval, parents and physicians now have a medicine to treat the underlying cause of cystic fibrosis in patients as young as 1 year of age. 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 cystic fibrosis.”

The approval was based on data yielded from the ongoing phase 3 open-label safety study (ARRIVAL), which involved 25 children aged 12 to <24 months with cystic fibrosis who have 1 of 10 mutations in the CFTR gene (G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D or R117H); the safety profile demonstrated in the study was consistent with that observed in previous phase 3 studies of older children and adults. The majority of adverse events ranged from mild to moderate in severity, with none of the patients discontinuing treatment. Only 2 patients experienced elevated liver enzymes greater than 8 times the upper limit of normal but continued ivacaftor treatment following a dose interruption. Cough (74%), pyrexia (37%), elevated aspartate aminotransferase (37%), elevated alanine aminotransferase (32%) and runny nose (32%) were listed as the most common adverse events (≥30%). In 2 patients, 4 serious adverse events were observed.

Furthermore, mean baseline sweat chloride for the children in this study was 104.1 mmol/L (n=14), and the mean sweat chloride level was 33.8 mmol/L (n=14) following 24 weeks of treatment with ivacaftor. A mean absolute change of -73.5 mmol/L was also observed in the 10 subjects with paired sweat chloride samples at baseline and week 24.

“I’m very excited about the approval of ivacaftor in children ages 12 to less than 24 months as this is the first regulatory approval of a CFTR modulator in this age group,” added Margaret Rosenfeld, MD, MPH, Seattle Children’s Research Institute and Department of Pediatrics, University of Washington School of Medicine, in the statement. “The premise of newborn screening for cystic fibrosis is to intervene very early in the course of disease with the goal of improving long term outcomes, so this is a significant milestone for parents and caregivers of young children with cystic fibrosis.”

Previously, ivacaftor was approved for the treatment of cystic fibrosis 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 in the United States. A Marketing Authorization Application for a line extension (ages 12 to <24 months) has been submitted to the European Medicines Agency by Vertex; a decision is expected in the first half of 2019.

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