BACKGROUND: Elexacaftor/tezacaftor/ivacaftor(ELX/TEZ/IVA) was safe and efficacious in children with CF 2-5y with at least one F508del allele in 24-week phase 3 Trial 445-111. Children who completed 445-111 were eligible for the long-term safety and efficacy extension trial. METHODS: This 2-part (part A and B), open-label, phase 3, 192-week trial enrolled children >/= 2y who completed 445-111. PRIMARY ENDPOINT: safety and tolerability. Secondary endpoints: absolute changes in sweat chloride(SwCl) concentration and lung clearance index 2.5(LCI(2.5)). 96-week analysis (Part A) is reported. RESULTS: Seventy children received ELX/TEZ/IVA and mean exposure was 89.9 (SD: 17.0) weeks. All children had >/=1 adverse event(AE), most AEs were mild (35.7%) or moderate (52.9%) in severity. Most AEs were generally consistent with known manifestations of CF in children. Fifteen children had >/=1 serious AE, of which 1 (DIOS) was considered related to ELX/TEZ/IVA. Three children discontinued due to AEs. Decreases in SwCl (-57.0 mmol/L [95%CI: -61.5, -52.6]) and LCI(2.5) (-0.90 [95%CI: -1.14, -0.67]) were sustained from parent trial baseline, 80.8% of children achieved SwCl<60 mmol/L (below diagnostic threshold) and 28.8% achieved SwCl<30 mmol/L (normal). Growth remained in normal range throughout treatment period. Increases in fecal elastase-1 from parent trial baseline were maintained through Week 96, with 9 children above the pancreatic sufficiency threshold. CONCLUSIONS: ELX/TEZ/IVA remained generally safe and well-tolerated in this extension trial. SwCl and lung function improvements reported in parent trial were maintained through additional 96 w of treatment. These results demonstrate long-term safety and efficacy, and CF disease-modifying potential of ELX/TEZ/IVA in children >/=2y.
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