A NEW 96-week study confirms the long-term safety and sustained efficacy of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) in children with cystic fibrosis aged 6–11 years and carrying F/MF genotypes.
This Phase 3b open-label extension trial followed participants who had completed a prior 24-week placebo-controlled study. Dosing was stratified by age and weight, with children under 30 kg receiving ELX 100 mg once daily, TEZ 50 mg once daily, and IVA 75 mg every 12 hours. Those 30 kg or more, or aged 12 and older, received ELX 200 mg, TEZ 100 mg, and IVA 150 mg on the same schedules. The primary outcome was safety and tolerability, with secondary outcomes including changes from parent study baseline in sweat chloride concentration, lung clearance index (LCI2.5), percent predicted FEV1 (ppFEV1), and the Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score.
Of the 120 children enrolled, 118 (98.3%) experienced adverse events (AEs), the majority of which were mild (43.3%) or moderate (48.3%) in severity. Common AEs included COVID-19 (58.3%), cough (51.7%), and nasopharyngitis (45.0%). Despite this, both children who transitioned from placebo and those who continued ELX/TEZ/IVA showed sustained clinical improvements at Week 96. Mean sweat chloride concentration decreased by -57.3 mmol·L-1 (95% CI: -61.6, -52.9) in the former placebo group and -57.5 mmol·L-1 (95% CI: -62.0, -53.0) in the continuous treatment group. LCI2.5 improved by -1.74 and -2.35 units respectively, while ppFEV1 increased by 6.1 and 6.9 percentage points. CFQ-R respiratory domain scores improved by 6.6 points for prior placebo recipients and 2.6 points in those already on treatment.
The findings confirm that ELX/TEZ/IVA is generally safe and well-tolerated in children over a 2-year period. These results support its continued use, showing durable improvements in lung function and quality of life in this young cystic fibrosis population.
Reference
Mall MA et al. Elexacaftor/tezacaftor/ivacaftor in children aged ≥6 years with cystic fibrosis heterozygous for F508del and a minimal function mutation: results from a 96-week open-label extension study. Eur Respir J. 2025; DOI:10.1183/13993003.02435-2024.
