Background: The safety and efficacy of 24 weeks of lumacaftor/ivacaftor combination therapy in children aged 6–11 years with cystic fibrosis homozygous for the F508del-CFTR mutation was previously demonstrated in two phase 3 studies. Here, we report long-term safety and efficacy data in children who rolled over from these two parent studies into a 96-week lumacaftor/ivacaftor open-label extension study (NCT02544451).
Methods: The primary endpoint was safety. Secondary endpoints included change from baseline in lung clearance index 2∙5% (LCI2·5), sweat chloride concentration, body mass index, and Cystic Fibrosis Questionnaire–Revised respiratory domain score.
Findings: Of 239 children who enrolled in the study and received at least one dose of lumacaftor/ivacaftor, 215 completed 96 weeks of treatment. Most children had adverse events (AEs) that were mild or moderate in severity, and there was a low rate of AEs leading to treatment discontinuation. The most frequently reported AEs were common manifestations or complications of cystic fibrosis or were consistent with the known safety profile of lumacaftor/ivacaftor in older children and adults. No new safety concerns were identified with extended lumacaftor/ivacaftor treatment. Children treated with placebo in the parent study and who began lumacaftor/ivacaftor in this extension study had improvements in efficacy endpoints consistent with those observed in the parent studies. Improvements observed in lumacaftor/ivacaftor-treated children in the parent studies were generally maintained in the extension study.
Interpretation: Lumacaftor/ivacaftor therapy in children homozygous for F508del-CFTR who initiated treatment at ages 6–11 years was generally safe and well tolerated, and efficacy was sustained for up to 120 weeks in this open-label extension study. These data support the long-term use of lumacaftor/ivacaftor to treat children aged ≥6 years homozygous for the F508del-CFTR mutation.