The preclinical discovery and development of the combination of ivacaftor + tezacaftor used to treat cystic fibrosis

New approaches to genetic therapies for cystic fibrosis

(2020) A. Christopher Boyd et al.   Journal of Cystic Fibrosis

CFTR Modulators: The Changing Face of Cystic Fibrosis in the Era of Precision Medicine

(2020) Miquéias Lopes-Pacheco   Frontiers in Pharmacology

Emerging Therapeutic Approaches for Cystic Fibrosis. From Gene Editing to Personalized Medicine

(2019) Iwona Pranke et al.   Frontiers in Pharmacology

Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis

(2019) Gitte Berkers et al.   Cell Reports

Two CFTR mutations within codon 970 differently impact on the chloride channel functionality

(2019) Felice Amato et al.   HUMAN MUTATION

Pharmacokinetic and Drug-Drug Interaction Profiles of the Combination of Tezacaftor/Ivacaftor

(2019) Varun Garg et al.   CTS-Clinical and Translational Science

Transcriptomic responses to Ivacaftor and prediction of Ivacaftor clinical responsiveness

(2019) Tao Sun et al.   AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY

An open-label extension study of ivacaftor in children with CF and a CFTR gating mutation initiating treatment at age 2–5 years (KLIMB)

(2019) Margaret Rosenfeld et al.   Journal of Cystic Fibrosis

Safety, pharmacokinetics, and pharmacodynamics of lumacaftor and ivacaftor combination therapy in children aged 2–5 years with cystic fibrosis homozygous for F508del-CFTR: an open-label phase 3 study

(2019) John J McNamara et al.   Lancet Respiratory Medicine

Clinically approved CFTR modulators rescue Nrf2 dysfunction in cystic fibrosis airway epithelia

(2019) Dana C. Borcherding et al.   JOURNAL OF CLINICAL INVESTIGATION

Theranostics by testing CFTR modulators in patient-derived materials: The current status and a proposal for subjects with rare CFTR mutations

(2019) Margarida D. Amaral et al.   Journal of Cystic Fibrosis

A phase 3 study of tezacaftor in combination with ivacaftor in children aged 6 through 11 years with cystic fibrosis

(2019) Seth Walker et al.   Journal of Cystic Fibrosis

ePS1.05 High reproducibility of Forskolin-induced swelling of intestinal organoids across three academic laboratories

(2019) P. van Mourik et al.   Journal of Cystic Fibrosis

ORKAMBI-Mediated Rescue of Mucociliary Clearance in Cystic Fibrosis Primary Respiratory Cultures Is Enhanced by Arginine Uptake, Arginase Inhibition, and Promotion of Nitric Oxide Signaling to the Cystic Fibrosis Transmembrane Conductance Regulator Channel

(2019) Yu-Sheng Wu et al.   MOLECULAR PHARMACOLOGY

Real-Life Safety and Effectiveness of Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis

(2019) Pierre-Régis Burgel et al.   AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

Unravelling the Regions of Mutant F508del-CFTR More Susceptible to the Action of Four Cystic Fibrosis Correctors

(2019) Amico et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Forskolin-induced swelling of intestinal organoids correlates with disease severity in adults with cystic fibrosis and homozygous F508del mutations

(2019) Karin M. de Winter – de Groot et al.   Journal of Cystic Fibrosis

Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial

(2019) Harry G M Heijerman et al.   LANCET

Elexacaftor–Tezacaftor–Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele

(2019) Peter G. Middleton et al.   NEW ENGLAND JOURNAL OF MEDICINE

Nanomolar-potency ‘co-potentiator’ therapy for cystic fibrosis caused by a defined subset of minimal function CFTR mutants

(2019) Puay-Wah Phuan et al.   Scientific Reports

Functional rescue of c.3846G>A (W1282X) in patient-derived nasal cultures achieved by inhibition of nonsense mediated decay and protein modulators with complementary mechanisms of action

(2019) Onofrio Laselva et al.   Journal of Cystic Fibrosis

Vx-809/Vx-770 treatment reduces inflammatory response to Pseudomonas aeruginosa in primary differentiated cystic fibrosis bronchial epithelial cells

(2018) Manon Ruffin et al.   AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY

Effects of Lumacaftor–Ivacaftor Therapy on Cystic Fibrosis Transmembrane Conductance Regulator Function in Phe508del Homozygous Patients with Cystic Fibrosis

(2018) Simon Y. Graeber et al.   AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR

(2018) Scott H. Donaldson et al.   AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

Lumacaftor/ivacaftor in patients with cystic fibrosis and advanced lung disease homozygous for F508del-CFTR

(2018) Jennifer L. Taylor-Cousar et al.   Journal of Cystic Fibrosis

Detection of CFTR function and modulation in primary human nasal cell spheroids

(2018) John J. Brewington et al.   Journal of Cystic Fibrosis

CFTR rescue with VX-809 and VX-770 favors the repair of primary airway epithelial cell cultures from patients with class II mutations in the presence of Pseudomonas aeruginosa exoproducts

(2018) Damien Adam et al.   Journal of Cystic Fibrosis

Recent progress in translational cystic fibrosis research using precision medicine strategies

(2018) Deborah M. Cholon et al.   Journal of Cystic Fibrosis

CFTR modulator theratyping: Current status, gaps and future directions

(2018) John Paul Clancy et al.   Journal of Cystic Fibrosis

Lipophilicity of the Cystic Fibrosis Drug, Ivacaftor (VX-770), and Its Destabilizing Effect on the Major CF-causing Mutation: F508del

(2018) Stephanie Chin et al.   MOLECULAR PHARMACOLOGY

Correctors of the Major Cystic Fibrosis Mutant Interact through Membrane-Spanning Domains

(2018) Onofrio Laselva et al.   MOLECULAR PHARMACOLOGY

Comprehensive mapping of cystic fibrosis mutations to CFTR protein identifies mutation clusters and molecular docking predicts corrector binding site

(2018) Steven V. Molinski et al.   PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS

Ivacaftor treatment of cystic fibrosis in children aged 12 to

(2018) Margaret Rosenfeld et al.   Lancet Respiratory Medicine

Structure-guided combination therapy to potently improve the function of mutant CFTRs

(2018) Guido Veit et al.   NATURE MEDICINE

Cost-Effectiveness and Budget Impact of Lumacaftor/Ivacaftor in the Treatment of Cystic Fibrosis

(2018) Pratyusha Vadagam et al.   Journal of Managed Care & Specialty Pharmacy

Isogenic cell models of cystic fibrosis-causing variants in natively expressing pulmonary epithelial cells

(2018) Hillary C. Valley et al.   Journal of Cystic Fibrosis

VX-445–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles

(2018) Dominic Keating et al.   NEW ENGLAND JOURNAL OF MEDICINE

VX-659–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles

(2018) Jane C. Davies et al.   NEW ENGLAND JOURNAL OF MEDICINE

Real-life acute lung function changes after lumacaftor/ivacaftor first administration in pediatric patients with cystic fibrosis

(2017) Aurélie Labaste et al.   Journal of Cystic Fibrosis

Immediate effects of lumacaftor/ivacaftor administration on lung function in patients with severe cystic fibrosis lung disease

(2017) Natalia Popowicz et al.   Journal of Cystic Fibrosis

Real-life initiation of lumacaftor/ivacaftor combination in adults with cystic fibrosis homozygous for the Phe508del CFTR mutation and severe lung disease

(2017) Dominique Hubert et al.   Journal of Cystic Fibrosis

Tezacaftor–Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis

(2017) Steven M. Rowe et al.   NEW ENGLAND JOURNAL OF MEDICINE

Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del

(2017) Jennifer L. Taylor-Cousar et al.   NEW ENGLAND JOURNAL OF MEDICINE

CFTR-dependent chloride efflux in cystic fibrosis mononuclear cells is increased by ivacaftor therapy

(2017) Lorenzo Guerra et al.   PEDIATRIC PULMONOLOGY

The diagnosis of cystic fibrosis

(2017) Kris De Boeck et al.   PRESSE MEDICALE

Correction of CFTR function in nasal epithelial cells from cystic fibrosis patients predicts improvement of respiratory function by CFTR modulators

(2017) Iwona M. Pranke et al.   Scientific Reports

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

(2017) Felix Ratjen et al.   Lancet Respiratory Medicine

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

(2017) Michael W Konstan et al.   Lancet Respiratory Medicine

Neutrophil Membrane Cholesterol Content is a Key Factor in Cystic Fibrosis Lung Disease

(2017) Michelle M. White et al.   EBioMedicine

Cystic Fibrosis and Its Management Through Established and Emerging Therapies

(2016) David R. Spielberg et al.   Annual Review of Genomics and Human Genetics

The investigational Cystic Fibrosis drug Trimethylangelicin directly modulates CFTR by stabilizing the first membrane-spanning domain

(2016) Onofrio Laselva et al.   BIOCHEMICAL PHARMACOLOGY

Low free drug concentration prevents inhibition of F508del CFTR functional expression by the potentiator VX-770 (ivacaftor)

(2016) Elizabeth Matthes et al.   BRITISH JOURNAL OF PHARMACOLOGY

Optimal correction of distinct CFTR folding mutants in rectal cystic fibrosis organoids

(2016) Johanna F. Dekkers et al.   EUROPEAN RESPIRATORY JOURNAL

Human pluripotent stem cell-derived acinar/ductal organoids generate human pancreas upon orthotopic transplantation and allow disease modelling

(2016) Meike Hohwieler et al.   GUT

Correctors and Potentiators Rescue Function of the Truncated W1282X-Cystic Fibrosis Transmembrane Regulator (CFTR) Translation Product

(2016) Peter M. Haggie et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Biomarkers for cystic fibrosis drug development

(2016) Marianne S. Muhlebach et al.   Journal of Cystic Fibrosis

Alterations in blood leukocytes of G551D-bearing cystic fibrosis patients undergoing treatment with ivacaftor

(2016) Preston E. Bratcher et al.   Journal of Cystic Fibrosis

Physiologic endpoints for clinical studies for cystic fibrosis

(2016) Sanja Stanojevic et al.   Journal of Cystic Fibrosis

Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis

(2016) Johanna F. Dekkers et al.   Science Translational Medicine

CFTR Modulators: Shedding Light on Precision Medicine for Cystic Fibrosis

(2016) Miquéias Lopes-Pacheco   Frontiers in Pharmacology

Treatment of cystic fibrosis in low-income countries

(2016) Malena Cohen-Cymberknoh et al.   Lancet Respiratory Medicine

Safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2–5 years with cystic fibrosis and a CFTR gating mutation (KIWI): an open-label, single-arm study

(2016) Jane C Davies et al.   Lancet Respiratory Medicine

Efficacy and safety of lumacaftor/ivacaftor combination therapy in patients with cystic fibrosis homozygous for Phe508del CFTR by pulmonary function subgroup: a pooled analysis

(2016) J Stuart Elborn et al.   Lancet Respiratory Medicine

Progress in therapies for cystic fibrosis

(2016) Kris De Boeck et al.   Lancet Respiratory Medicine

Precision Medicine: At What Price?

(2015) Thomas Ferkol et al.   AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

Antibiotic therapy affects functional behaviour in cystic fibrosis blood mononuclear cells

(2015) Lorenzo Guerra et al.   EUROPEAN RESPIRATORY JOURNAL

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

(2015) Claire E. Wainwright et al.   NEW ENGLAND JOURNAL OF MEDICINE

Personalized medicine for cystic fibrosis: Establishing human model systems

(2015) Hongmei Mou et al.   PEDIATRIC PULMONOLOGY

Efficacy and safety of ivacaftor in patients with cystic fibrosis who have an Arg117His-CFTR mutation: a double-blind, randomised controlled trial

(2015) Richard B Moss et al.   Lancet Respiratory Medicine

Cystic fibrosis

(2015) Felix Ratjen et al.   Nature Reviews Disease Primers

A neutrophil intrinsic impairment affecting Rab27a and degranulation in cystic fibrosis is corrected by CFTR potentiator therapy

(2014) K. Pohl et al.   BLOOD

Efficacy and safety of ivacaftor in patients with cystic fibrosis and a non-G551D gating mutation

(2014) Kris De Boeck et al.   Journal of Cystic Fibrosis

Cystic fibrosis genetics: from molecular understanding to clinical application

(2014) Garry R. Cutting   NATURE REVIEWS GENETICS

Some gating potentiators, including VX-770, diminish  F508-CFTR functional expression

(2014) G. Veit et al.   Science Translational Medicine

Potentiator ivacaftor abrogates pharmacological correction of  F508 CFTR in cystic fibrosis

(2014) D. M. Cholon et al.   Science Translational Medicine

A CFTR corrector (lumacaftor) and a CFTR potentiator (ivacaftor) for treatment of patients with cystic fibrosis who have a phe508del CFTR mutation: a phase 2 randomised controlled trial

(2014) Michael P Boyle et al.   Lancet Respiratory Medicine

Efficacy and Safety of Ivacaftor in Patients Aged 6 to 11 Years with Cystic Fibrosis with aG551DMutation

(2013) Jane C. Davies et al.   AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

Corrector VX-809 stabilizes the first transmembrane domain of CFTR

(2013) Tip W. Loo et al.   BIOCHEMICAL PHARMACOLOGY

WS7.3 VX-661, an investigational CFTR corrector, in combination with ivacaftor, a CFTR potentiator, in patients with CF and homozygous for the F508Del-CFTR mutation: Interim analysis

(2013) S. Donaldson et al.   Journal of Cystic Fibrosis

Effect of ivacaftor on CFTR forms with missense mutations associated with defects in protein processing or function

(2013) Fredrick Van Goor et al.   Journal of Cystic Fibrosis

VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane-spanning domain 1

(2013) Hong Yu Ren et al.   MOLECULAR BIOLOGY OF THE CELL

Mechanism-based corrector combination restores ΔF508-CFTR folding and function

(2013) Tsukasa Okiyoneda et al.   Nature Chemical Biology

A functional CFTR assay using primary cystic fibrosis intestinal organoids

(2013) Johanna F Dekkers et al.   NATURE MEDICINE

Ivacaftor treatment of cystic fibrosis patients with the G551D mutation: a review of the evidence

(2013) Kavitha Kotha et al.   Therapeutic Advances in Respiratory Disease

Personalized Medicine in Cystic Fibrosis

(2012) John P. Clancy et al.   AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

Requirements for Efficient Correction of ΔF508 CFTR Revealed by Analyses of Evolved Sequences

(2012) Juan L. Mendoza et al.   CELL

Correction of Both NBD1 Energetics and Domain Interface Is Required to Restore ΔF508 CFTR Folding and Function

(2012) Wael M. Rabeh et al.   CELL

Ivacaftor in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del-CFTR Mutation

(2012) Patrick A. Flume et al.   CHEST

Innate immunity in cystic fibrosis lung disease

(2012) D. Hartl et al.   Journal of Cystic Fibrosis

A CFTR Potentiator in Patients with Cystic Fibrosis and theG551DMutation

(2011) Bonnie W. Ramsey et al.   NEW ENGLAND JOURNAL OF MEDICINE

Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809

(2011) F. Van Goor et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for theF508del-CFTRmutation

(2011) J P Clancy et al.   THORAX

Influence of cell background on pharmacological rescue of mutant CFTR

(2010) Nicoletta Pedemonte et al.   AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY

Effect of VX-770 in Persons with Cystic Fibrosis and the G551D-CFTRMutation

(2010) Frank J. Accurso et al.   NEW ENGLAND JOURNAL OF MEDICINE

ΔF508 CFTR processing correction and activity in polarized airway and non-airway cell monolayers

(2010) S.M. Rowe et al.   PULMONARY PHARMACOLOGY & THERAPEUTICS

Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770

(2009) F. Van Goor et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Clinical phenotype of cystic fibrosis patients with the G551D mutation

(2009) D.M. Comer et al.   QJM-AN INTERNATIONAL JOURNAL OF MEDICINE

Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice

(2008) C. Castellani et al.   Journal of Cystic Fibrosis

Evidence-Based Practice Recommendations for Nutrition-Related Management of Children and Adults with Cystic Fibrosis and Pancreatic Insufficiency: Results of a Systematic Review

(2008) Virginia A. Stallings et al.   JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION