After 25 years of intensive search, there is not yet a cure for cystic fibrosis (CF). However, the quest has led to major breakthroughs in understanding the basic disease defect and defining strategies to correct it. The first cystic fibrosis transmembrane conductance regulator (CFTR) modulators have been introduced in clinic. Some show an impressive clinical benefit, like the potentiator ivacaftor for the 4% of patients with a class III defect. Others offer at present only a limited benefit, like the combination corrector lumacaftor plus potentiator ivacaftor for subjects homozygous for F508del. These findings prove that the basic defect in CF can be modified and hold the promise that one day CF will no longer be a life-shortening disease.
Conclusion: This review updates the clinician on recent achievements as well as on the CF research pipeline.
What is known: Cystic fibrosis (CF) is a common and life-shortening disease that currently cannot be cured. However, for each of the six CF mutation classes, disease-modifying drugs are under way.
What is new: This review is a concise update for the clinician on new drugs that reached the CF clinical pipeline. The research strategies in CF have become a paradigm for clinical trials in other inherited diseases.
Keywords: CFTR; Clinical trials; Corrector; Cystic fibrosis; N-of-1 trial; Organoids; Potentiator.