S67 Effects of tezacaftor/ivacaftor (TEZ/IVA) treatment in patients heterozygous for F508del-CFTR and a residual function mutation: patient-reported outcomes in a phase 3 randomized, controlled trial (EXPAND)

Introduction and objectives To examine the treatment effect of TEZ/IVA on disease-related symptoms, functioning, and well-being as measured by Cystic Fibrosis Questionnaire–Revised (CFQ-R) in patients heterozygous for F508del and a second allele with a CFTR mutation predicted to have residual function ( F508del /RF). Improvement in the respiratory domain of CFQ-R has been reported previously. Here, we report the other health domains of CFQ-R. Methods TEZ/IVA (100 mg QD/150 mg BID) was evaluated vs placebo in patients aged ≥12 years with CF and F508del /RF in EXPAND (NCT02392234), a Phase 3, randomized, double-blind, placebo-controlled, crossover design trial. CFQ-R consists of 12 domains, including respiratory symptoms (EXPAND key secondary endpoint), and was assessed at baseline, and weeks 4 and 8. In the prespecified analysis, a linear mixed-effects model was used to estimate mean absolute change in each domain score from baseline to the average of week 4 and 8 scores. In the post hoc analysis, cumulative distribution functions (CDF) were used to compare distribution of change in scores from baseline to week 8 between TEZ/IVA vs placebo. No multiplicity adjustment was used. CDF differences were assessed using the Anderson-Darling test (nominal P value). Results Data from 244 patients with a baseline CFQ-R assessment were included in the prespecified analysis; patients with baseline and week 8 scores (n=240) were included in the post hoc analysis. In the prespecified analysis, a TEZ/IVA treatment effect, vs placebo, was observed in health perceptions, vitality, physical functioning, role functioning, social functioning, weight, treatment burden, and emotional functioning (table 1). Post hoc CDF analysis demonstrated consistent findings in a subset of domains (8/12), including respiratory symptoms, health perceptions, vitality, physical functioning, role functioning, social functioning, treatment burden, and body image (all p Conclusions Treatment with TEZ/IVA demonstrated improvement in patient-reported health outcomes beyond respiratory symptoms in CF patients with F508del /RF. These findings highlight the treatment impact on patients’ functioning and further support the overall value of TEZ/IVA treatment benefit. Abstract previously submitted to the North American Cystic Fibrosis Conference, Denver, CO, 18–20 October, 2018. Sponsored by Vertex Pharmaceuticals Incorporated