Tezacaftor and ivacaftor for the treatment of cystic fibrosis

Introduction: Cystic fibrosis (CF) is a complex, multi-system, genetic disease affecting over 70,000 people worldwide. The underlying defect is a mutation in the CFTR gene. Dysfunctional CFTR protein results in abnormal anion movement across epithelial membranes in affected organs. There has been a paradigm shift in CF treatment over the last decade with the advent of CFTR modulation, treatments which target this underlying genetic defect and have the potential to change the course of CF clinical disease. Areas covered: Available CFTR modulators in current clinical practice are reviewed in this article, with a direct comparison and summary of relevant pivotal clinical trials. The approval of ivacaftor and subsequent development of lumacaftor and tezacaftor dual combinations represents an exciting development in CF management in recent years. Expert opinion: Tezacaftor/ivacaftor (tez/iva) appears to have a more favorable adverse event and drug-drug interaction profile than lumacaftor/ivacaftor. Tez/iva has been approved, alongside Phe508del, for a large number of 'residual function' CFTR mutations, with some based on response to in vitro culture. Dual therapy with tez/iva has paved the way for triple CFTR modulation currently in clinical trials with an ultimate view to provide modulation therapy to the majority of CF genotypes in the future.