Tezacaftor–ivacaftor in residual-function heterozygotes with cystic fibrosis

New England Journal of Medicine

Volumn 377, Issue 21, 2017, Pages 2024-2035

  Rowe, Steven M ^a   Daines, Cori ^b   Ringshausen, Felix C ^c   Kerem, Eitan ^d   Wilson, John ^e   Tullis, Elizabeth ^f   Nair, Nitin ^g   Simard, Christopher ^g   Han, Linda ^g   Ingenito, Edward P ^g   McKee, Charlotte ^g   Lekstrom Himes, Julie ^g   Davies, Jane C ^h  

^a University of Alabama at Birmingham   (United States)

^b UNIVERSITY OF ARIZONA   (United States)

^c HANNOVER MEDICAL SCHOOL   (Germany)

^d HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^e ALFRED HEALTH   (Australia)

^f ST MICHAEL'S HOSPITAL   (Canada)

^g VERTEX PHARMACEUTICALS   (United States)

^h ROYAL BROMPTON AND HAREFIELD NHS FOUNDATION TRUST   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CREATINE KINASE; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; IVACAFTOR; PHENYLALANINE; PLACEBO; TEZACAFTOR; 1,3 BENZODIOXOLE DERIVATIVE; AMINOPHENOL DERIVATIVE; CFTR PROTEIN, HUMAN; INDOLE DERIVATIVE; QUINOLONE DERIVATIVE;

ADOLESCENT; ADULT; ARTICLE; CFTR GENE; CHILD; CONTROLLED STUDY; COUGHING; CREATINE KINASE BLOOD LEVEL; CROSSOVER PROCEDURE; CYSTIC FIBROSIS; DIARRHEA; DISEASE EXACERBATION; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DRUG WITHDRAWAL; DYSPNEA; FATIGUE; FEMALE; FEVER; FORCED EXPIRATORY VOLUME; GENE; GENE FUNCTION; GENE MUTATION; HEADACHE; HEMOPTYSIS; HETEROZYGOTE; HUMAN; INCREASE SPUTUM PRODUCTION; INDEL MUTATION; LUNG INFECTION; MAJOR CLINICAL STUDY; MALE; MISSENSE MUTATION; MONOTHERAPY; NAUSEA; NOSE OBSTRUCTION; OROPHARYNX PAIN; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; QUALITY OF LIFE ASSESSMENT; RANDOMIZED CONTROLLED TRIAL; RESPIRATORY TRACT DISEASE; RHINOPHARYNGITIS; TREATMENT DURATION; CLINICAL TRIAL; DRUG COMBINATION; DRUG EFFECTS; GENETICS; MULTICENTER STUDY; MUTATION; PATHOPHYSIOLOGY; QUALITY OF LIFE; YOUNG ADULT;

ADOLESCENT; ADULT; AMINOPHENOLS; BENZODIOXOLES; CHILD; CROSS-OVER STUDIES; CYSTIC FIBROSIS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; DOUBLE-BLIND METHOD; DRUG COMBINATIONS; FEMALE; FORCED EXPIRATORY VOLUME; HETEROZYGOTE; HUMANS; INDOLES; MALE; MUTATION; QUALITY OF LIFE; QUINOLONES; YOUNG ADULT;

EID: 85034732149     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMoa1709847     Document Type: Article

References (32)

1. Elborn JS. Cystic fibrosis. Lancet 2016; 388:2519-31.
2. O’Sullivan BP, Freedman SD. Cystic fibrosis. Lancet 2009;373:1891-904.
3. CFTR2.org. Clinical and functional translation of CFTR. Baltimore: Johns Hopkins University (http://www.cftr2.org/).
4. Castellani C, Cuppens H, Macek M Jr, et al. Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. J Cyst Fibros 2008;7: 179-96.
5. Clancy JP, Jain M. Personalized medicine in cystic fibrosis: dawning of a new era. Am J Respir Crit Care Med 2012;186: 593-7.
6. Van Goor F, Yu H, Burton B, Hoffman BJ. Effect of ivacaftor on CFTR forms with missense mutations associated with defects in protein processing or function. J Cyst Fibros 2014;13:29-36.
7. McKone EF, Emerson SS, Edwards KL, Aitken ML. Effect of genotype on phenotype and mortality in cystic fibrosis: a retrospective cohort study. Lancet 2003; 361:1671-6.
8. Comer DM, Ennis M, McDowell C, et al. Clinical phenotype of cystic fibrosis patients with the G551D mutation. QJM 2009; 102:793-8.
9. Rodman DM, Polis JM, Heltshe SL, et al. Late diagnosis defines a unique population of long-term survivors of cystic fibrosis. Am J Respir Crit Care Med 2005;171:621-6.
10. Van Goor F, Hadida S, Grootenhuis P. Pharmacological rescue of mutant CFTR function for the treatment of cystic fibrosis. In: Fermini B, Priest BT, eds. Topics in medicinal chemistry: ion channels. Berlin: Springer, 2008:91-120.
11. Davies JC, Cunningham S, Harris WT, et al. Safety, pharmacokinetics, and phar-macodynamics of ivacaftor in patients aged 2-5 years with cystic fibrosis and a CFTR gating mutation (KIWI): an open-label, single-arm study. Lancet Respir Med 2016;4:107-15.
12. Ramsey BW, Davies J, McElvaney NG, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med 2011;365:1663-72.
13. Rowe SM, McColley SA, Rietschel E, et al. Lumacaftor/ivacaftor treatment of patients with cystic fibrosis heterozygous for F508del-CFTR. Ann Am Thorac Soc 2017;14:213-9.
14. Davies J, Sheridan H, Bell N, et al. Assessment of clinical response to ivacaftor with lung clearance index in cystic fibrosis patients with a G551D-CFTR mutation and preserved spirometry: a randomised controlled trial. Lancet Respir Med 2013; 1:630-8.
15. 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;5: 557-67.
16. Van Goor F, Hadida S, Grootenhuis PD, et al. Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proc Natl Acad Sci U S A 2011;108:18843-8.
17. Wainwright CE, Elborn JS, Ramsey BW, et al. Lumacaftor–ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR. N Engl J Med 2015;373: 220-31.
18. Yu YC, Sohma Y, Hwang TC. On the mechanism of gating defects caused by the R117H mutation in cystic fibrosis transmembrane conductance regulator. J Physiol 2016;594:3227-44.
19. Pilewski J, Higgins M, Cooke J, Nick JA. EPS1.5: a phase 3 extension study evaluating the safety and efficacy of long-term ivacaftor (IVA) in patients with cystic fibrosis (CF) and phenotypic or molecular evidence of residual CFTR function. J Cyst Fibros 2017;16:Suppl 1: S37. abstract.
20. Donaldson S, Pilewski J, Griese M, et al. Tezacaftor/ivacaftor in patients with cystic fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR. Am J Respir Crit Care Med 2017 September 20 (Epub ahead of print).
21. Wang X, Dockery DW, Wypij D, Fay ME, Ferris BG Jr. Pulmonary function between 6 and 18 years of age. Pediatr Pul-monol 1993;15:75-88.
22. Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am J Respir Crit Care Med 1999;159:179-87.
23. Quittner AL, Modi AC, Wainwright C, Otto K, Kirihara J, Montgomery AB. Determination of the minimal clinically important difference scores for the Cystic Fibrosis Questionnaire-Revised respiratory symptom scale in two populations of patients with cystic fibrosis and chronic Pseudomonas aeruginosa airway infection. Chest 2009;135:1610-8.
24. Konstan MW, McKone EF, Moss RB, et al. Assessment of safety and efficacy of long-term treatment with combination lumacaftor and ivacaftor therapy in patients with cystic fibrosis homozygous for the F508del-CFTR mutation (PROGRESS): a phase 3, extension study. Lancet Respir Med 2017;5:107-18.
25. Milla CE, Ratjen F, Marigowda G, Liu F, Waltz D, Rosenfeld M. Lumacaftor/ivacaftor in patients aged 6-11 years with cystic fibrosis and homozygous for F508del-CFTR. Am J Respir Crit Care Med 2017;195:912-20.
26. Moss RB, Flume PA, Elborn JS, et al. Efficacy and safety of ivacaftor in patients with cystic fibrosis who have an Arg117His-CFTR mutation: a double-blind, randomised controlled trial. Lancet Respir Med 2015;3: 524-33.
27. Goss CH, Quittner AL. Patient-reported outcomes in cystic fibrosis. Proc Am Thorac Soc 2007;4:378-86.
28. Van Goor F. Nonclinical profile of the CFTR corrector VX-661. Presented at the 30th annual North American Cystic Fibrosis Conference, Orlando, FL, October 27–29, 2016. (Poster.)
29. Accurso FJ, Rowe SM, Clancy JP, et al. Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. N Engl J Med 2010;363:1991-2003.
30. Courville CA, Tidwell S, Liu B, Accurso FJ, Dransfield MT, Rowe SM. Acquired defects in CFTR-dependent β-adrenergic sweat secretion in chronic obstructive pulmonary disease. Respir Res 2014;15:25.
31. Wilschanski M, Dupuis A, Ellis L, et al. Mutations in the cystic fibrosis transmembrane regulator gene and in vivo transepithelial potentials. Am J Respir Crit Care Med 2006;174:787-94.
32. Taylor-Cousar JL, Munck A, McKone EF, et al. Tezacaftor–ivacaftor in patients with cystic fibrosis homozygous for Phe508del. N Engl J Med 2017;377:2013-23.