Tezacaftor/ivacaftor in subjects with cystic fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR

American Journal of Respiratory and Critical Care Medicine

Volumn 197, Issue 2, 2018, Pages 214-224

  Donaldson, Scott H ^a   Pilewski, Joseph M ^b   Griese, Matthias ^c   Cooke, Jon ^d   Viswanathan, Lakshmi ^e   Tullis, Elizabeth ^f   Davies, Jane C ^g,h   Lekstrom Himes, Julie A ^d   Wang, Linda T ^e  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^c LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^d Vertex Pharmaceuticals Ltd   (United Kingdom)

^e VERTEX PHARMACEUTICALS   (United States)

^f ST MICHAEL'S HOSPITAL   (Canada)

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

^h Biostatistics Limited   (United Kingdom)

Author keywords

CFTR modulator; Cystic fibrosis transmembrane conductance regulator corrector; Forced expiratory volume; Sweat chloride

Indexed keywords

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

ADULT; ARTHRITIS; ARTICLE; CONTROLLED STUDY; COUGHING; CYSTIC FIBROSIS; DIARRHEA; DOUBLE BLIND PROCEDURE; DRUG DOSE ESCALATION; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG SAFETY; FATIGUE; FEMALE; FOLLOW UP; HEADACHE; HUMAN; MALE; MONOTHERAPY; MULTICENTER STUDY; NAUSEA; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROOF OF CONCEPT; RANDOMIZED CONTROLLED TRIAL; SPUTUM; THERAPY; ADOLESCENT; CLINICAL TRIAL; COMBINATION DRUG THERAPY; DOSE RESPONSE; DRUG ADMINISTRATION; GENETICS; LUNG FUNCTION TEST; MAXIMUM TOLERATED DOSE; MOLECULARLY TARGETED THERAPY; ORAL DRUG ADMINISTRATION; PROCEDURES; PROGNOSIS; RISK ASSESSMENT; SEVERITY OF ILLNESS INDEX; TREATMENT OUTCOME; YOUNG ADULT;

ADMINISTRATION, ORAL; ADOLESCENT; ADULT; AMINOPHENOLS; BENZODIOXOLES; CYSTIC FIBROSIS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG ADMINISTRATION SCHEDULE; DRUG THERAPY, COMBINATION; FEMALE; HUMANS; INDOLES; MALE; MAXIMUM TOLERATED DOSE; MOLECULAR TARGETED THERAPY; PROGNOSIS; QUINOLONES; RESPIRATORY FUNCTION TESTS; RISK ASSESSMENT; SEVERITY OF ILLNESS INDEX; TREATMENT OUTCOME; YOUNG ADULT;

EID: 85045190321     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.201704-0717OC     Document Type: Article

References (30)

1. Cutting GR Cystic fibrosis genetics: from molecular understanding to clinical application. Nat Rev Genet 2015; 16:45-56.
2. Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z, et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 1989; 245: 1066-1073.
3. Kerem B, Rommens JM, Buchanan JA, Markiewicz D, Cox TK, Chakravarti A, et al. Identification of the cystic fibrosis gene: genetic analysis. Science 1989; 245:1073-1080.
4. Rommens JM, Iannuzzi MC, Kerem B, Drumm ML, Melmer G, Dean M, et al. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 1989; 245:1059-1065.
5. Derichs N. Targeting a genetic defect: cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis. Eur Respir Rev 2013; 22:58-65.
6. Cystic Fibrosis Foundation. Patient registry: annual data report 2014. Bethesda, MD: Cystic Fibrosis Foundation; 2015 [accessed 2016 May 25]. Available from: https://www.cff.org/2014-Annual-Data-Report/.
7. Farinha CM, Amaral MD. Most F508del-CFTR is targeted to degradation at an early folding checkpoint and independently of calnexin. Mol Cell Biol 2005; 25:5242-5252.
8. Jensen TJ, Loo MA, Pind S, Williams DB, Goldberg AL, Riordan JR. Multiple proteolytic systems, including the proteasome, contribute to CFTR processing. Cell 1995; 83:129-135.
9. Lukacs GL, Chang XB, Bear C, Kartner N, Mohamed A, Riordan JR, et al. The DF508 mutation decreases the stability of cystic fibrosis transmembrane conductance regulator in the plasma membrane: determination of functional half-lives on transfected cells. J Biol Chem 1993; 268:21592-21598.
10. Sharma M, Benharouga M, Hu W, Lukacs GL. Conformational and temperature-sensitive stability defects of the DF508 cystic fibrosis transmembrane conductance regulator in post-endoplasmic reticulum compartments. J Biol Chem 2001; 276:8942-8950.
11. Flume PA, Liou TG, Borowitz DS, Li H, Yen K, Ordoñez CL, et al.; VX 08-770-104 Study Group. Ivacaftor in subjects with cystic fibrosis who are homozygous for the F508del-CFTR mutation. Chest 2012; 142:718-724.
12. Clancy JP, Rowe SM, Accurso FJ, Aitken ML, Amin RS, Ashlock MA, et al. Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for the F508del-CFTR mutation. Thorax 2012; 67:12-18.
13. Wainwright CE, Elborn JS, Ramsey BW. Lumacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR. N Engl J Med 2015; 373:1783-1784.
14. U.S. Food and Drug Administration. FDA expands approved use of Kalydeco to treat additional mutations of cystic fibrosis; 2017 [accessed 2017 Jul 5]. Available from: https://cysticfibrosisnewstoday.com/kalydeco-ivacaftor/.
15. Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Dřevínek P, et al.; VX08-770-102 Study Group. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med 2011; 365: 1663-1672.
16. De Boeck K, Munck A, Walker S, Faro A, Hiatt P, Gilmartin G, et al. Efficacy and safety of ivacaftor in patients with cystic fibrosis and a non-G551D gating mutation. J Cyst Fibros 2014; 13:674-680.
17. Moss RB, Flume PA, Elborn JS, Cooke J, Rowe SM, McColley SA, et al.; VX11-770-110 (KONDUCT) Study Group. 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; 3:524-533.
18. Davies JC, Wainwright CE, Canny GJ, Chilvers MA, Howenstine MS, Munck A, et al.; VX08-770-103 (ENVISION) Study Group. Efficacy and safety of ivacaftor in patients aged 6 to 11 years with cystic fibrosis with a G551D mutation. Am J Respir Crit Care Med 2013; 187:1219-1225.
19. Orkambi [package insert]. Boston, MA: Vertex Pharmaceuticals Incorporated; 2016.
20. Donaldson S, Pilewski J, Cooke J, Lekstrom-Himes J. Addition of VX-661, an investigational CFTR corrector, to ivacaftor, a CFTR potentiator, in patients with CF and heterozygous for F508del/G551D-CFTR [Poster 260]. Presented at the 28th Annual North American Cystic Fibrosis Conference. October 9-11, 2014, Atlanta, GA.
21. Pilewski J, Donaldson S, Cooke J, Lekstrom-Himes J. Phase 2 studies reveal additive effects of VX-661, and investigational CFTR corrector, and ivacaftor, a CFTR potentiator, in patients with CF who carry the F508del-CFTR mutation [abstract S10.4]. Pediatric Pulmonol 2014; 49(Suppl 38):S157.
22. Pilewski JM, Cooke J, Lekstrom-Himes J, Donaldson S; VX-661 Investigator Groups. VX-661 in combination with ivacaftor in patients with cystic fibrosis and the F508del-CFTR mutation [abstract WS01.4]. J Cyst Fibros 2014; 14(Suppl 1):S1.
23. Rosenstein BJ, Cutting GR; Cystic Fibrosis Foundation Consensus Panel. The diagnosis of cystic fibrosis: a consensus statement. J Pediatr 1998; 132:589-595.
24. Knudson RJ, Lebowitz MD, Holberg CJ, Burrows B. Changes in the normal maximal expiratory flow-volume curve with growth and aging. Am Rev Respir Dis 1983; 127:725-734.
25. Kalydeco [package insert]. Boston, MA: Vertex Pharmaceuticals Incorporated; 2017.
26. Wainwright CE, Elborn JS, Ramsey BW, Marigowda G, Huang X, Cipolli M, et al.; TRAFFIC Study Group; TRANSPORT Study Group. Lumacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR. N Engl J Med 2015; 373:220-231.
27. Hubert D, Chiron R, Camara B, Grenet D, Prévotat A, Bassinet L, et al. Real-life initiation of lumacaftor/ivacaftor combination in adults with cystic fibrosis homozygous for the Phe508del CFTR mutation and severe lung disease. J Cyst Fibros 2017; 16:388-391.
28. Jennings MT, Dezube R, Paranjape S, West NE, Hong G, Braun A, et al. An observational study of outcomes and tolerances in patients with cystic fibrosis initiated on lumacaftor/ivacaftor. Ann Am Thorac Soc 2017; 14:1662-1666.
29. Konstan MW, McKone EF, Moss RB, Marigowda G, Tian S, Waltz D, 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; 5:107-118.
30. Labaste A, Ohlmann C, Mainguy C, Jubin V, Perceval M, Coutier L, et al. Real-life acute lung function changes after lumacaftor/ivacaftor first administration in pediatric patients with cystic fibrosis. J Cyst Fibros 2017; 16:709-712.