Long-term safety and efficacy of Lumacaftor/Ivacaftor in children 12 months of age and older with cystic fibrosis: a 96-week open-label study

AIMS We evaluated long-term safety and efficacy of lumacaftor/ivacaftor (LUM/IVA) in children age 12 to <24 months with cystic fibrosis (CF) homozygous for F508del . METHODS This international, 96-week, phase 3, open-label study enrolled children who completed parent study 809-122 (after 2-week washout) or were LUM/IVA naïve. Primary endpoint was safety and tolerability. Secondary efficacy endpoint was change from baseline in sweat chloride concentration. RESULTS Fifty-two children (39 from 809-122; 13 LUM/IVA naïve) participated. Mean exposure to LUM/IVA was 597 ( sd , 162) days. All children had ≥1 adverse event (AE), which were mostly mild (32.7%) or moderate (55.8%) in severity and consistent with common manifestations of CF or early childhood illnesses. One child (1.9%) discontinued study drug due to a treatment-emergent AE of increased alanine/aspartate aminotransferases that resolved after discontinuation. Twelve children (23.1%) had serious AEs, none of which was considered related to LUM/IVA. At week 96, mean absolute change from pretreatment baseline in sweat chloride concentration was −21.0 (95% CI, −27.6 to −14.3) mmol·L −1 . Growth parameters, which did not significantly change, were in the normal range throughout the 96-week treatment period. Improvements from baseline were observed in mean fecal elastase-1, fecal calprotectin, and serum immunoreactive trypsinogen. CONCLUSIONS Lumacaftor/ivacaftor remained generally safe and well-tolerated over 96 weeks. Improvements in sweat chloride concentration and markers of pancreatic function and intestinal inflammation were consistent with the parent study. These results demonstrate the long-term safety and efficacy of LUM/IVA in the 12 to 24-month-old population.