The future of CFTR modulating therapies for cystic fibrosis

Huge progress has been made over the last few years in the field of small molecule therapies targeting cystic fibrosis transmembrane conductance regulator (CFTR), the protein defective in patients with cystic fibrosis. This review describes the progress and areas of future research.

Ivacaftor is the first drug of its kind to be licensed for clinical use in patients with a number of mutations resulting in defective gating (opening). For patients with more common mutations, characterized by misfolding, a combination approach is required with both corrector drugs which allow the protein to correctly localize and potentiators to improve protein function. A number of other CFTR modulators are at earlier stages of clinical development.

With the advent of such precision medicine, patient genotype is now highly relevant. Areas of current unmet need include drugs to cover all mutation classes, increasing access to younger children with the design of rational and tailored clinical trials, and ensuring equality of access globally.