FDA Expands CF Drug Kalydeco to Children as Young as Age 1 Year

Megan Brooks

August 17, 2018

The US Food and Drug Administration (FDA) has expanded the indication for the cystic fibrosis (CF) drug ivacaftor (Kalydeco, Vertex Pharmaceuticals) to children as young as 12 months who have at least one mutation in the CF transmembrane conductance regulator (CFTR) gene that is responsive to the drug, as determined on the basis of clinical or in vitro assay data.

Ivacaftor is already approved in the United States for the treatment of CF in patients aged 2 years and older who have ivacaftor-responsive mutations in the CFTR gene.

CF is a rare, life-shortening genetic disease that affects approximately 75,000 people in North America, Europe, and Australia. The disease is caused by a defective or missing CFTR protein resulting from mutations in the CFTR gene. Ivacaftor works by helping a defective CFTR protein better regulate secretion viscosity, which improves lung function of patients with CF, as well as other effects of CF.

The expanded approval is based on data from an ongoing phase 3 open-label safety study of 25 children aged 12 to <24 months who had CF and who had one of 10 mutations in the CFTR gene.

The study showed that the drug's safety profile in patients of this age was consistent with that seen in other phase 3 studies involving older children and adults, the company said. Most adverse events were mild or moderate in severity, and in no patient was the drug discontinued because of adverse events.

In two patients, liver enzyme levels were greater than eight times the upper limit of normal, but the children continued to receive ivacaftor after a dose interruption. The most common adverse events (≥30%) were cough (74%), pyrexia (37%), elevated aspartate aminotransferase level (37%), elevated alanine aminotransferase level (32%), and runny nose (32%). Four serious adverse events were observed in two patients.

As for efficacy, mean baseline sweat chloride for 14 children in the study was 104.1 mmol/L. After 24 weeks of ivacaftor treatment, the mean sweat chloride level fell to 33.8 mmol/L. For the 10 patients, paired sweat chloride samples at baseline and at week 24 demonstrated a mean absolute change of -73.5 mmol/L.

The data were presented at the European Cystic Fibrosis Society conference in June and were published in Lancet Respiratory Medicine last month.

"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," said Margaret Rosenfeld, MD, of Seattle Children's Research Institute and University of Washington School of Medicine, in a company news release.

"The premise of newborn screening for CF 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 CF," said Rosenfeld.

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