Vertex Pharmaceuticals Incorporated has announced positive results from an open-label phase 3 study of Kalydeco (ivacaftor) in children with cystic fibrosis (CF) ages 1 to 2 years who have one of 10 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The ARRIVAL study met its primary endpoint of safety, showing that ivacaftor was generally well tolerated, and safety data were consistent with those seen in previous phase 3 studies of ivacaftor in children ages 2 to 5 years and 6 to 11 years. There was also a substantial improvement in sweat chloride, a secondary endpoint, as well as in multiple exploratory endpoints evaluating pancreatic function. These data suggest the potential to modify the course of CF in children as young as one year of age. The study is ongoing in infants younger than one year old.

Based on these results, Vertex plans to submit applications for ivacaftor in children ages 1 to 2 years to the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in the first quarter of 2018.

"We know that cystic fibrosis is a progressive disease with organ damage already present at birth, so the earlier patients can begin treatment, the greater their potential for improved outcomes," said Jane Davies, M.D., Royal Brompton Hospital and Imperial College, London, co-lead investigator of the ARRIVAL study. "These results are incredibly exciting: they suggest that we can begin treating the underlying cause of cystic fibrosis with Kalydeco in children as young as one year of age."

"We have a significant body of evidence demonstrating Kalydeco's immediate and long-term benefits and its potential to modify the course of CF," said Jeffrey Chodakewitz, M.D., Executive Vice President and Chief Medical Officer at Vertex. "These results are an important step in our goal of treating children as early as possible to intervene in this progressive disease."

Kalydeco is currently approved by the FDA for the treatment of CF in patients ages 2 and older who have one of 38 ivacaftor-responsive mutations in the CFTR gene.

ARRIVAL is an ongoing 2-part, open-label Phase 3 study assessing ivacaftor in children with CF younger than 2 years of age who have one of the following ten mutations in the CFTR gene: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D or R117H. Part A of the study is evaluating the safety and pharmacokinetics of ivacaftor for five days to support the evaluation of ivacaftor for 24 weeks in Part B of the study. Part B is evaluating the safety, pharmacokinetics and efficacy of ivacaftor for 24 weeks. The primary endpoint of Part B of the study is safety, and secondary endpoints include pharmacokinetics and absolute change in sweat chloride. There are several exploratory endpoints, including ones evaluating pancreatic function. Data reported today are from Part B of the study in children ages 1 to 2 years; Parts A and B of the study in infants younger than one year old are ongoing. Of the 18 children who completed Part B of the 24-week study, 17 enrolled in a rollover study to continue receiving ivacaftor treatment. The only participant not to continue in the rollover study was older than 2 years of age, so elected to begin treatment with commercial ivacaftor.