[New therapies for cystic fibrosis targeting the CFTR gene or the CFTR protein].

BACKGROUND: The treatment of cystic fibrosis has been symptom-based for a number of years. New therapies that aim to improve CFTR protein function are now emerging.

CURRENT SCIENTIFIC KNOWLEDGE: The results of gene therapy has been modest but a recent clinical trial shows a positive effect on FEV1. Recent research has focused primarily on CFTR protein function. Significant respiratory improvement (an average 10% FEV1 increase and a decrease in the frequency of exacerbations) has been achieved with ivacaftor, a CFTR potentiator, in patients with gating mutations, resulting in its marketing authorization (in 2012 for the G551D mutation and in 2015 for rarer mutations). In phe508del homozygous patients, the combination of ivacaftor with a CFTR corrector (lumacaftor) has also led to respiratory improvement, albeit less impressive. The effectiveness of ataluren in patients with nonsense mutations is being evaluated.

OUTLOOK: New CFTR correctors and potentiators are being developed. CFTR protein therapy could change the course of the disease but cost/effectiveness issues should not be overlooked.

CONCLUSION: Ivacaftor can be prescribed in CF patients with a class 3 mutation from the age of 6 years. The Orkambi(®) will soon be available for homozygous phe508del patients from the age of 12 years.