Lumacaftor–Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR

• Published in: The New England journal of medicine Vol. 373; no. 3; pp. 220 - 231
• Main Authors: Wainwright, Claire E, Elborn, J. Stuart, Ramsey, Bonnie W, Marigowda, Gautham, Huang, Xiaohong, Cipolli, Marco, Colombo, Carla, Davies, Jane C, De Boeck, Kris, Flume, Patrick A, Konstan, Michael W, McColley, Susanna A, McCoy, Karen, McKone, Edward F, Munck, Anne, Ratjen, Felix, Rowe, Steven M, Waltz, David, Boyle, Michael P
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 16-07-2015
• Subjects: Adolescent; Adult; Aminophenols - administration & dosage; Aminophenols - adverse effects; Aminopyridines - administration & dosage; Aminopyridines - adverse effects; Antibiotics; Benzodioxoles - administration & dosage; Benzodioxoles - adverse effects; Child; Conductance; Cystic fibrosis; Cystic Fibrosis - drug therapy; Cystic Fibrosis - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Double-Blind Method; Drug therapy; Drug Therapy, Combination; Female; Forced Expiratory Volume - drug effects; Homozygote; Hospitalization - statistics & numerical data; Humans; Intravenous administration; Male; Middle Aged; Mutation; Patients; Proteins; Quinolones - administration & dosage; Quinolones - adverse effects; Young Adult; United States > US
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1409547

This study identified a new combination therapy for patients with cystic fibrosis homozygous for the Phe508del CFTR mutation. Treatment with ivacaftor, a CFTR potentiator, and lumacaftor, a CFTR corrector, resulted in improvement in pulmonary function and clinical status.
Cystic fibrosis is a genetic disease that is associated with high rates of premature death.
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–
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It is a multisystem disease that is characterized by pancreatic insufficiency and chronic airway infections associated with loss of lung function, repeated pulmonary exacerbations, and, ultimately, respiratory failure.
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Cystic fibrosis is caused by gene mutations that result in deficient or dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) protein, an anion channel that is normally present in the epithelial membrane. Phe508del (c.1521_1523delCTT; formerly F508del) is the most common
CFTR
mutation; approximately 45% of patients with cystic fibrosis are homozygous for this allele.
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Cystic fibrosis is . . .