Elexacaftor/tezacaftor/ivacaftor in children aged 6 and older with cystic fibrosis and at least 1 F508del allele: Interim results from a Phase 3 open-label extension study

Abstract

Background: Elexacaftor/tezacaftor/ivacaftor and ivacaftor was shown to be safe and efficacious in children aged 6 to 11 with cystic fibrosis (CF) homozygous for F508del-CFTR or heterozygous for F508del-CFTR and a minimal-function CFTR mutation in a 24-week pivotal study (NCT03691779) [1]. Here we report results from the week 24 interim analysis of an ongoing, 96-week, Phase 3, open-label extension (OLE) of the pivotal study designed to assess the long-term safety and efficacy of elexacaftor/tezacaftor/ivacaftor in children aged 6 and older (NCT04183790). Methods: Children weighing 30 kg or more receive the full adult dose (elexacaftor 200 mg once daily, tezacaftor 100 mg once daily, and ivacaftor 150 mg every 12 hours), and thoseweighing less than 30 kg receive 50% of the adult dose. The primary endpoint is safety and tolerability. Secondary endpoints include absolute changes in ppFEV1, sweat chloride, Cystic Fibrosis Questionnaire-Revised respiratory domain score, BMI and associated z score, and lung clearance index2.5. Data collection for theWeek 24 interim analysis was based on the date that the last participant reached Week 24. Results: Sixty-four children entered this OLE of the 24-week pivotal study. At the time of the interim analysis, mean duration of exposure to elexacaftor/tezacaftor/ivacaftor in the OLE was 39.2 weeks. Adverse events (AEs) were reported for 51 children (79.7%), all of which were mild or moderate in severity and generally consistent with manifestations of CF. No children have discontinued study drug because of AEs in the OLE. Overall, the children in this OLE study experienced robust and clinically meaningful improvements in efficacy endpoints, consistent with the pivotal study. Compared to the pivotal study baseline, elexacaftor/ tezacaftor/ivacaftor treatment improved ppFEV1 (9.5 percentage points; standard error [SE] 1.3), SwCl (−64.7 mmol/L; SE 1.7), Cystic Fibrosis Questionnaire-Revised respiratory domain score (12.9 points; SE 1.2), BMI (1.27 kg/m2; SE 0.15), BMI z score (0.34; SE 0.06), and lung clearance index2.5 (−1.91; SE 0.18) at the OLE Week 24 interim analysis. Conclusion: Interim results at Week 24 of this OLE study are consistent with the previously established safety profile of elexacaftor/tezacaftor/ ivacaftor in children aged 6 and older. The robust and clinically meaningful improvements in lung function, respiratory symptoms, and systemic CFTR activity indicate that elexacaftor/tezacaftor/ivacaftor provides long-term benefit in this younger patient population.L20149183412021-12-03 <br />