Cystic fibrosis (CF) is the most common autosomal recessive disorder among Caucasians affecting ~70,000 people worldwide. The lack of functional cystic fibrosis transmembrane conductance regulator (CFTR) causes dysregulation of epithelial fluid transport in the lungs, gastrointestinal tract, and sweat glands. Areas covered: The most common disease-causing CFTR mutation, F508del, is present in over 75% of those affected;. therapies targeting F508del function have the promise to reduce morbidity and mortality in the majority of patients with CF. The combination of lumacaftor, which corrects the aberrant intracellular trafficking of F508del, and ivacaftor, which potentiates CFTR function, is known as OrkambiTM, and is the first drug approved for the treatment of CF in patients who are F508del-homozygotes. OrkambiTM is currently approved for use in children aged 2 and older based on recent data from open-label Phase 3 clinical safety studies. Expert opinion: OrkambiTM modestly improves clinical outcomes for people with CF who are F508del-homozygotes, and does so with a reasonable safety profile. This is a major advance in therapy for CF, but further advances are needed, perhaps with the addition of a third agent to this combination small molecule therapy, in order to expand both the targeted population and beneficial effects.
Keywords: Cystic fibrosis; Orkambi; ivacaftor; lumacaftor.
Efficacy and safety of lumacaftor and ivacaftor in patients aged 6-11 years with cystic fibrosis homozygous for F508del-CFTR: a randomised, placebo-controlled phase 3 trial.Lancet Respir Med. 2017 Jul;5(7):557-567. doi: 10.1016/S2213-2600(17)30215-1. Epub 2017 Jun 9. Lancet Respir Med. 2017. PMID: 28606620 Clinical Trial.
Efficacy of lumacaftor-ivacaftor for the treatment of cystic fibrosis patients homozygous for the F508del-CFTR mutation.Expert Rev Precis Med Drug Dev. 2016;1(3):235-243. doi: 10.1080/23808993.2016.1175299. Epub 2016 Apr 22. Expert Rev Precis Med Drug Dev. 2016. PMID: 27482545 Free PMC article.
Lumacaftor/Ivacaftor in Patients Aged 6-11 Years with Cystic Fibrosis and Homozygous for F508del-CFTR.Am J Respir Crit Care Med. 2017 Apr 1;195(7):912-920. doi: 10.1164/rccm.201608-1754OC. Am J Respir Crit Care Med. 2017. PMID: 27805836 Free PMC article. Clinical Trial.
Lumacaftor/ivacaftor, a novel agent for the treatment of cystic fibrosis patients who are homozygous for the F580del CFTR mutation.Expert Rev Clin Pharmacol. 2017 Oct;10(10):1055-1072. doi: 10.1080/17512433.2017.1378094. Epub 2017 Sep 22. Expert Rev Clin Pharmacol. 2017. PMID: 28891346 Review.
Lumacaftor and ivacaftor in the management of patients with cystic fibrosis: current evidence and future prospects.Ther Adv Respir Dis. 2015 Dec;9(6):313-26. doi: 10.1177/1753465815601934. Epub 2015 Sep 28. Ther Adv Respir Dis. 2015. PMID: 26416827 Review.