Tezacaftor for the treatment of cystic fibrosis

Expert Rev Respir Med. 2018 Sep;12(9):725-732. doi: 10.1080/17476348.2018.1507741. Epub 2018 Aug 9.


Cystic fibrosis (CF) is the most common, life-limiting autosomal recessive disease in Caucasians, and is caused by defects in production of the CFTR ion channel. Until recently, there were no available treatments targeting the disease-causing defects in CFTR but newly developed CFTR modulators are changing the course of disease in CF. The newest modulator, tezacaftor, is a CFTR corrector that was recently approved by the FDA to be used in combination with the first approved CFTR potentiator, ivacaftor. Areas covered: A detailed review of the clinical trials and published literature, focusing on safety and efficacy, leading to the approval of tezacaftor in CF. Expert commentary: Recent trials have demonstrated that the combination of tezacaftor-ivacaftor is a slightly superior combination to its predecessor, lumacaftor-ivacaftor, with respect to an increase in FEV1, adverse event profile, and drug-drug interactions. It is also approved for a large number of non-F508del, residual function mutations that are predicted to respond based on in vitro testing. The horizon for continued improvements in CFTR-targeted treatments is promising, with three-drug combinations currently in Phase 3 clinical trials, and other drugs with novel mechanisms of action being studied. Within the next 5 years, the vast majority of patients with CF are expected to have a modulator approved for their genotype.

Keywords: CFTR; Cystic fibrosis; tezacaftor.

Publication types

  • Review

MeSH terms

  • Aminophenols / therapeutic use
  • Aminopyridines / therapeutic use
  • Benzodioxoles / therapeutic use*
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis / physiopathology
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Drug Combinations
  • Genotype
  • Humans
  • Indoles / therapeutic use*
  • Mutation
  • Quinolones / therapeutic use


  • Aminophenols
  • Aminopyridines
  • Benzodioxoles
  • Drug Combinations
  • Indoles
  • Quinolones
  • lumacaftor, ivacaftor drug combination
  • tezacaftor
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • ivacaftor