Lumacaftor + Ivacaftor (Efficacy)
The LUM/IVA is a combination of lumacaftor and ivacaftor and acts as a cystic fibrosis transmembrane conductance regulator (CFTR) enhancer. LUM/IVA is indicated for the treatment of cystic fibrosis (CF) in patients over 6 years of age that are homozygous for the F508del mutation of the CFTR gene. If a patient's genotype is unknown, mutational CF analysis should be performed as recommended by the Food and Drug Administration (FDA).
In in vitro studies, lumacaftor increases the amount of functional protein on the surface of the epithelial cell, apparently by partial correction of the folding defect of the protein that conditions the F508del mutation, avoiding the premature degradation of the same before completing its transport until the apical surface of the epithelial cell. Ivacaftor increases the channel opening time through the action of the protein present on the apical surface of the epithelial cell. Together, this translates into an increase in chlorine transport. However, the exact mechanism by which both drugs achieve this effect is unknown.
BRAND NAME:
Orkambi®
Genes analyzed
Bibliography
Barry PJ, Mall MA, Alvarez A, et al.Triple Therapy for Cystic Fibrosis Phe508del-Gating and -Residual Function Genotypes. N Engl J Med. 2021 Aug 26;385(9):815-825.
Egan ME.Effects of Lumacaftor/Ivacaftor in a Pediatric Cohort Homozygous for F508del-CFTR. Am J Respir Crit Care Med. 2017 Apr 1;195(7):849-850.
Labaste A, Ohlmann C, Mainguy C, et al.Real-life acute lung function changes after lumacaftor/ivacaftor first administration in pediatric patients with cystic fibrosis. J Cyst Fibros. 2017 Nov;16(6):709-712.
Ratjen F, Hug C, Marigowda G, et al.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.
