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Lumacaftor/Ivacaftor: A Review in Cystic Fibrosis

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Abstract

Lumacaftor/ivacaftor (Orkambi™) is a fixed-dose tablet containing a corrector (lumacaftor) and potentiator (ivacaftor) of the cystic fibrosis transmembrane conductance regulator (CFTR) and is the first therapy approved to treat the underlying cause of cystic fibrosis in patients (aged ≥12 years) homozygous for the most common CFTR mutation, F508del. Lumacaftor improves the processing of F508del CFTR and its transport to the cell surface, while ivacaftor increases the channel’s open probability and transport of chloride. In two 24-week trials in the approved patient population (TRAFFIC and TRANSPORT), lumacaftor 400 mg plus ivacaftor 250 mg, administered every 12 h in combination with standard therapy, was associated with an ≈3 % statistically significant improvement in lung function relative to placebo (as measured by the percent predicted forced expiratory volume in 1 s). Lumacaftor plus ivacaftor did not significantly improve respiratory symptoms, although reduced pulmonary exacerbations to a clinically meaningful extent and, in one trial (TRANSPORT), significantly improved body mass index (BMI). In an ongoing extension of these studies (PROGRESS), lumacaftor plus ivacaftor provided clinical benefit over a further 72 weeks of treatment. Lumacaftor plus ivacaftor had an acceptable tolerability profile, with the most common adverse events being respiratory or gastrointestinal in nature. Thus, lumacaftor/ivacaftor expands the treatment options available for patients with cystic fibrosis homozygous for the F508del-CFTR mutation, although its precise place in clinical practice remains to be determined.

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Acknowledgments

During the peer review process, the manufacturer of lumacaftor/ivacaftor was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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    Emma D. Deeks

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  1. Emma D. Deeks
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Correspondence to Emma D. Deeks.

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The preparation of this review was not supported by any external funding.

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Emma Deeks is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

Additional information

The manuscript was reviewed by: B. Bosch, Department of Paediatric Pulmonology, University Hospitals Leuven, Leuven, Belgium; L. J. Galietta, U.O.C. Genetica Medica, Istituto Giannina Gaslini, Genova, Italy; A. M. Jones, Manchester Adult Cystic Fibrosis Centre, University Hospitals South Manchester NHS Foundation Trust, Manchester, UK.

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Deeks, E.D. Lumacaftor/Ivacaftor: A Review in Cystic Fibrosis. Drugs 76, 1191–1201 (2016). https://doi.org/10.1007/s40265-016-0611-2

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