Long-term safety and efficacy of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis heterozygous for F508del-CFTR and a gating or residual function mutation

Background: The triple combination regimen of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be safe and efficacious in people with CF aged ≥ 12 years with cystic fibrosis (CF) and heterozygous for F508del-CFTR and either a CFTR gating mutation (F508del-gating genotypes) or residual function mutation (F508del-residual function genotypes). A 96-week Phase 3, open-label extension study was conducted to assess long-term safety and efficacy in these participants. Methods: Participants received ELX 200 mg once daily/TEZ 100 mg once daily/IVA 150 mg every 12 hours. The primary endpoint was safety and tolerability; secondary endpoints included absolute changes in percent predicted FEV1 (ppFEV1), sweat chloride concentration, body mass index (BMI) and associated z-score, body weight, and Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score. The annualized rate of change in ppFEV1 was assessed as a post hoc analysis. Results: 251 participants (F508del-gating genotypes, n=92; F508del-residual function genotypes, n=159) were enrolled and dosed. The last patient visit will take place on April 8, 2022. Results from primary and secondary endpoints and post hoc analysis will be presented. Sponsor: Vertex Pharmaceuticals Incorporated