Safety and Efficacy of Ivacaftor in Infants with Cystic Fibrosis Aged Between 1 and 4 Months

Ivacaftor, a CFTR protein potentiator, improves its function by increasing the channel opening activity on the cell surface in patients with cystic fibrosis (CF). Several clinical studies have demonstrated its safety and efficacy in children with pathogenetic variants of CFTR from 4 months of age onwards, showing early and lasting improvements in lung function, CFTR, and respiratory symptoms. Pancreatic function and growth parameters improve in children treated with Ivacaftor, strongly supporting the potential for early treatment to modify disease progression.

ARRIVAL is a phase 3 study that evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of Ivacaftor in children with CF under 24 months of age. The study was divided into cohorts based on age. Here, we report the results of the cohort of infants aged between 1 and less than 4 months, the youngest patient population to receive CFTR modulator therapy. Since Ivacaftor is a sensitive substrate of CYP3A, and CYP3A maturation is not well defined in infants, a low dose was initially administered, later adjusted based on individual pharmacokinetic results to ensure safe dosing. After dose adjustment, the mean plasma concentrations of Ivacaftor and its metabolites were within the range of previous clinical experience in older children, adolescents, and adults.

Ivacaftor was found to be safe and well tolerated, achieving rapid and clinically significant improvements in CFTR function, pancreatic function, intestinal inflammation, and growth parameters during the 24-week treatment period.

BIBLIOGRAPHY

McNally P, Singh A, McColley SA, Davies JC, Higgins M, Liu M, Lu J, Rodriguez-Romero V, Shih JL, Rosenfeld M; VX15-770-124 Study Group. Safety and efficacy of ivacaftor in infants aged 1 to less than 4 months with cystic fibrosis. J Cyst Fibros. 2024 Apr 4:S1569-1993(24)00042-0. doi: 10.1016/j.jcf.2024.03.012. Epub ahead of print. PMID: 38580563.