Cystic fibrosis in an era of genomically guided therapy

Hum Mol Genet. 2012 Oct 15;21(R1):R66-71. doi: 10.1093/hmg/dds345. Epub 2012 Aug 21.


Although affecting only 4-5% of those with cystic fibrosis (CF), the G551D-CFTR mutation is the target of the recently approved 'orphan drug', ivacaftor. The promise of such genomically guided therapies heralds a new era in the management of CF. A phase 3 trial demonstrated significant improvements in forced expiratory volume in 1 s (FEV(1)) from baseline, average weight gain, concentration in sweat chloride and reductions in pulmonary exacerbations [Ramsey, B.W., et al. A CFTR potentiator in patients with CF and the G551D mutation. N. Engl. J. Med., 2011. 365: 1663-1672.)]. Ivacaftor is among a group of recently approved, novel, mutation guided 'orphan drug' therapies that have established clinical benefits within their respective disease categories. They do not, however, offer a cure. Pharmaceutical and biotech companies have leveraged the incentivized benefits of the Orphan Drug Act to develop more of these drugs for orphan disorders affecting populations of <200 000 patients. With marked clinical efficacy via DNA sequence guidance, these drugs have also set a precedent in terms of the substantial annual costs and if this trend continues, such expenditures may become unsustainable. This paper explores the genomic pathophysiology of CF and how therapies such as ivacaftor provide benefit to those with the disease but at a considerably elevated price point.

Publication types

  • Review

MeSH terms

  • Aminophenols / economics
  • Aminophenols / therapeutic use*
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / economics
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Genetic Predisposition to Disease
  • Humans
  • Molecular Targeted Therapy / economics*
  • Mutation
  • Orphan Drug Production* / economics
  • Quinolones / economics
  • Quinolones / therapeutic use*


  • Aminophenols
  • CFTR protein, human
  • Quinolones
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • ivacaftor