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Profile of lumacaftor/ivacaftor combination: potential in the treatment of cystic fibrosis

Authors Arends A, Pettit R

Received 11 June 2015

Accepted for publication 14 July 2015

Published 14 August 2015 Volume 2015:5 Pages 61—68


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Lise Aagaard

Alexandria M Arends,1 Rebecca S Pettit2

1Department of Pharmacy, Indiana University Health, 2Department of Pharmacy, Riley Hospital for Children, Indianapolis, IN, USA

Objective: To review the cystic fibrosis transmembrane conductance regulator (CFTR) modulator ivacaftor in combination with lumacaftor for the treatment of cystic fibrosis (CF).
Data sources: Literature was accessed through MEDLINE (1977–June 2015) and national conference abstracts. Search terms included ivacaftor, VX-770, lumacaftor, VX-809, CFTR modulator, and CF.
Data synthesis: CF is an autosomal recessive genetic disease that affects chloride transport into and out of cells, causing the body to produce a thick, sticky mucus. There are over 1,800 CFTR mutations that have been identified and classified into six groups. CFTR modulators lumacaftor and ivacaftor are being studied in combination for the treatment of CF patients. This combination has proved beneficial for CF patients who are homozygous for the F508del mutation. In patients 12 years of age and older, the lumacaftor/ivacaftor combination demonstrated modest improvements in lung function with decreases in pulmonary exacerbation rate. There were clinically significant reductions in exacerbations, hospitalizations, and intravenous antibiotic requirement. Body mass index and Cystic Fibrosis Questionnaire-Revised scores were also positively impacted by therapy. A Phase I study evaluated the pharmacokinetics, safety, and tolerability of lumacaftor/ivacaftor in CF patients 6–11 years old. The combination is being further studied in this age group for clinical efficacy. The combination was generally well tolerated among all age groups, with the most common adverse events including headache and cough.
Conclusion: The use of lumacaftor in combination with ivacaftor in CF patients homozygous for the F508del mutation has shown improvement in percent predicted forced expiratory volume in 1 second and a decrease in the number of exacerbations. The combination was recently approved by the US Food and Drug Administration for homozygous F508del patients ≥12 years old. Studies are ongoing with this combination in younger patients as well as other CFTR modulators.

Keywords: cystic fibrosis, ivacaftor, lumacaftor, orkambi, VX-770, VX-809

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