lumacaftor (VX-809) / Vertex 
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 9 Diseases   1 Trial   1 Trial   672 News 


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  • ||||||||||  Kalydeco (ivacaftor) / Vertex, lumacaftor (VX-809) / Vertex, Orkambi (lumacaftor/ivacaftor) / Vertex
    Modeling Cystic Fibrosis (CF) with Induced Pluripotent Stem Cells (PENNSYLVANIA CONVENTION CENTER, Room 115 A-B (100 Level)) -  Mar 15, 2020 - Abstract #ATS2020ATS_4465;    
    We generated an iPSC bank of 18 extreme phenotypes and 3 typical CF patients, and 7 syngeneic pairs +/-CFTR correction which can be differentiated into airway epithelium as either 3D or 2D in vitro models in which CFTR function can be quantified for disease modeling, interrogating candidate modifiers, or predicting individualized drug responses. We plan to 1)assess the effect of CFTR on airway epithelium and 2)study the epithelial function of extreme-phenotype patients and contributions of alternative ion channels, which may advance treatment for this disease.
  • ||||||||||  lumacaftor (VX-809) / Vertex, Orkambi (lumacaftor/ivacaftor) / Vertex
    Ivacaftor or Lumacaftor/Ivacaftor Treatment Does Not Alter the Core CF Airway Epithelial Gene Response to Rhinovirus (PHILADELPHIA MARRIOTT DOWNTOWN, Grand Ballroom Salon H-J (Level 5)) -  Mar 15, 2020 - Abstract #ATS2020ATS_2816;    
    These results suggest CFTR modulators do not interfere with core airway epithelial responses to rhinovirus infection, but in Class 2 CFTR mutations modulator therapy may ameliorate inherently defective biological pathways which contribute to worse viral infection outcomes in CF. Future work will assess these responses in differentiated CF epithelium and across fungal and bacterial respiratory pathogens.
  • ||||||||||  Kalydeco (ivacaftor) / Vertex, lumacaftor (VX-809) / Vertex, Orkambi (lumacaftor/ivacaftor) / Vertex
    Clinical, Journal:  Impact of CFTR-modulating drugs on GH-IGF-1 axis impairment in adult patients with cystic fibrosis. (Pubmed Central) -  Mar 8, 2020   
    Future work will assess these responses in differentiated CF epithelium and across fungal and bacterial respiratory pathogens. The pituitary gland may be damaged by CF disease and could benefit of the action of correcting drugs.
  • ||||||||||  lumacaftor (VX-809) / Vertex
    Journal:  Activity of lumacaftor is not conserved in zebrafish Cftr bearing the major cystic fibrosis-causing mutation. (Pubmed Central) -  Mar 4, 2020   
    Surprisingly, lumacaftor failed to rescue misprocessing of the F507del-zCftr at either 37 or 27°C suggesting that future comparative studies with F508del-hCFTR would provide insight into its structure: function relationships. Interestingly, the robust rescue of F508del-zCftr at 27°C and availability of methods for in vivo screening in zebrafish present the opportunity to define the cellular pathways underlying rescue.
  • ||||||||||  lumacaftor (VX-809) / Vertex
    Journal:  Hsp70 and DNAJA2 limit CFTR levels through degradation. (Pubmed Central) -  Mar 3, 2020   
    MKT077 also boosted the channel activity of ΔF508-CFTR when combined with the corrector compound VX809. Thus, the Hsp70 system is the major determinant of CFTR degradation, and its modulation can partially relieve the misfolding phenotype.
  • ||||||||||  Symdeko (tezacaftor/ivacaftor) / Vertex, elexacaftor (VX-445) / Vertex, Trikafta (elexacaftor/tezacaftor/ivacaftor) / Vertex
    Journal:  Elexacaftor/tezacaftor/ivacaftor (Trikafta) for cystic fibrosis. (Pubmed Central) -  Feb 15, 2020   
    This review covers the contemporary clinical and scientific knowledge base for small molecule CFTR modulator drug therapy, gene delivery vectors and CRISPR/Cas9 gene editing and highlights the prospect of these technologies for future treatment options. No abstract available
  • ||||||||||  lumacaftor (VX-809) / Vertex, Farydak (panobinostat) / Novartis, Istodax (romidepsin) / Astellas, BMS
    Journal:  HDAC Inhibitors Rescue Multiple Disease-Causing CFTR Variants. (Pubmed Central) -  Feb 9, 2020   
    We further demonstrate a synergistic effect of these HDACi with Vx809, that can significantly restore channel activity for multiple CFTR variants. These data suggest that HDACi can serve to level the cellular playing field for correcting CF-causing mutations, a leveling effect that might also extend to other protein misfolding diseases.
  • ||||||||||  lumacaftor (VX-809) / Vertex, Orkambi (lumacaftor/ivacaftor) / Vertex
    Journal:  Lumacaftor-ivacaftor in the treatment of cystic fibrosis: design, development and place in therapy. (Pubmed Central) -  Feb 7, 2020   
    Perhaps more importantly, those treated report increased levels of well-being and their rate of respiratory exacerbations is significantly improved. This review traces the development and use of this combination of CFTR modulators, the first licensed drug for treating the homozygous p.Phe508del CF genotype at the intracellular level by correcting the protein defect.
  • ||||||||||  Kalydeco (ivacaftor) / Vertex, lumacaftor (VX-809) / Vertex
    Preclinical, Journal:  Characterization of two rat models of cystic fibrosis-KO and F508del CFTR-Generated by Crispr-Cas9. (Pubmed Central) -  Jan 18, 2020   
    Exposure of F508del CFTR nasal primary cultures to a combination of VX-809 and VX-770 improved CFTR-mediated Cl transport. The F508del rats reproduce the phenotypes observed in CFTR KO animals and represent a novel resource to advance the development of CF therapeutics.
  • ||||||||||  lumacaftor (VX-809) / Vertex
    Journal:  Molecular docking analysis of timepidium with Acetylcholine and lumacaftor with GABA(A) activator. (Pubmed Central) -  Jan 8, 2020   
    Therefore, it is of interest to design and develop inhibitors for these targets. Hence, we describe the molecular binding features of timepidium with acetylcholine and lumacaftor with GABA(A) activator using molecular docking based geometric optimization and screening analysis for further consideration.
  • ||||||||||  Kalydeco (ivacaftor) / Vertex, lumacaftor (VX-809) / Vertex, Orkambi (lumacaftor/ivacaftor) / Vertex
    Journal:  Chronic β2AR stimulation limits CFTR activation in human airway epithelia. (Pubmed Central) -  Dec 6, 2019   
    β-Agonist-induced CFTR dysfunction was sufficient to abrogate VX809/VX770 modulation of F508del-CFTR in vitro. Understanding the clinical relevance of our observations is critical for CF patients using these drugs, and for investigators to inform future CFTR modulator drug trials.
  • ||||||||||  Journal:  Physiological and pharmacological characterization of the N1303K mutant CFTR. (Pubmed Central) -  Dec 6, 2019   
    These results suggest a defective function of the NBDs in N1303K-CFTR. An improvement of channel function by GLPG1837 or VX-770 and an increase of Band C protein by VX-809 or VX-661 support a therapeutic strategy of combining CFTR potentiator and corrector for patients carrying the N1303K mutation.
  • ||||||||||  lumacaftor (VX-809) / Vertex
    Journal:  Rescue of CFTR NBD2 mutants N1303K and S1235R is influenced by the functioning of the autophagosome. (Pubmed Central) -  Dec 6, 2019   
    Confocal microscopic studies showed that the N1303K and S1235R mutant proteins both co-localized with LC3, but this co-localization was abolished by the corrector combination and, to a lesser extent, by VX-809...After treatment with correctors persistent degradation by the autophagosome may limit restoration of function. Thus, mutations in NBD2 of CFTR, in contrast to ΔF508-CFTR, may require additional personalized strategies to rescue them.
  • ||||||||||  lumacaftor (VX-809) / Vertex, Orkambi (lumacaftor/ivacaftor) / Vertex
    Clinical, Journal:  Lumacaftor/ivacaftor in patients with cystic fibrosis and advanced lung disease homozygous for F508del-CFTR. (Pubmed Central) -  Nov 15, 2019   
    P3b
    Compared with patients with higher lung function, respiratory events were more common in patients with ppFEV1<40; aside from these events, the lumacaftor/ivacaftor safety profile was consistent with previous studies. Results suggest that patients with ppFEV1<40 may benefit from treatment initiation at a lower dose with augmented monitoring before increasing to the full dose.
  • ||||||||||  lumacaftor (VX-809) / Vertex, Orkambi (lumacaftor/ivacaftor) / Vertex
    Clinical, Journal:  Effect of Lumacaftor/Ivacaftor on glucose metabolism and insulin secretion in Phe508del homozygous cystic fibrosis patients. (Pubmed Central) -  Nov 15, 2019   
    The investigation could not demonstrate that treatment with Lumacaftor/Ivacaftor had a consistent impact on glucose tolerance and insulin secretion. Further adequately-powered studies examining glucose metabolism are needed to properly evaluate drug response in the endocrine pancreas and to test whether this treatment could eventually prevent the development of cystic fibrosis-related diabetes (CFRD).
  • ||||||||||  lumacaftor (VX-809) / Vertex
    Journal:  -Cyclodextrins Reduce the Ability of Pseudomonas Outer Membrane Vesicles to Reduce CFTR Cl Secretion. (Pubmed Central) -  Nov 14, 2019   
    Our data suggest that HPbCD, which is in clinical trials for Niemann-Pick Type C disease, and MbCD, which has been approved by the FDA for use in solubilizing lipophilic drugs, may enhance the clinical efficacy of VX-809 in CF patients when added to the apical side of airway epithelial cells, and reduce planktonic growth and biofilm formation by Pseudomonas aeruginosa. Both effects would be beneficial to CF patients.
  • ||||||||||  LONGER-TERM PULMONARY OUTCOMES OF CFTR MODULATOR THERAPY (104) -  Nov 11, 2019 - Abstract #NACFC2019NACFC_52;    
    Data sources such as patient registries are invaluable tools for such evaluations, but they must be supplemented with rigorous prospective studies of outcomes not commonly included in clinical trials. Such research is essential to enable clinicians to provide optimal care, particularly as more therapies are developed in the future.
  • ||||||||||  PTI-801 / Proteostasis
    CURRENT STATUS OF THE PROTEOSTASIS THERAPEUTICS CFTR MODULATOR DEVELOPMENT PROGRAM (205) -  Nov 11, 2019 - Abstract #NACFC2019NACFC_50;    
    P1/2
    Similarly, in vitro CFTR activity of the triple combination of PTI 801 and PTI 808 with the PTI 428 amplifier is superior to that seen with tezacaftor/ivacaftor in combination with VX-659 (corrector) in homozygous and heterozygous F508del cell cultures (data to be presented)...A phase 2 study is currently ongoing to evaluate the effects of PTI 808 in combination with PTI 801, with or without PTI 428, over a 28-day treatment period in CF subjects who are either homozygous or heterozygous for the F508del CFTR genotype. The goal is to initiate a phase 3 study in 2020.
  • ||||||||||  Symdeko (tezacaftor/ivacaftor) / Vertex, PTI-428 / Proteostasis
    INITIAL RESULTS EVALUATING THE FIRST-IN-CLASS CFTR AMPLIFIER, PTI-428, IN SUBJECTS WITH CF ON BACKGROUND TREATMENT WITH TEZACAFTOR/ IVACAFTOR () -  Nov 11, 2019 - Abstract #NACFC2019NACFC_24;    
    Treatment with PTI-428 led to an increase in CFTR protein production of approximately 50% in subjects with CF on background treatment with tezacaftor/ivacaftor, similar to that seen with PTI-428 plus lumacaftor/ivacaftor. Subject selection may explain the differential impact of PTI-428 on ppFEV1 on backgrounds of lumacaftor/ivacaftor versus tezacaftor/ivacaftor, and thus provides an important example of possible selection bias in the current era of the availability of multiple CFTR modulators.
  • ||||||||||  Symdeko (tezacaftor/ivacaftor) / Vertex, Kalydeco (ivacaftor) / Vertex, lumacaftor (VX-809) / Vertex
    CFTR MRNA EXPRESSION ANALYSIS UTILIZING A REPOSITORY OF BANKED PRIMARY AIRWAY EPITHELIAL SAMPLES () -  Nov 11, 2019 - Abstract #NACFC2019NACFC_19;    
    Studies are also planned to test impact of specific modulator treatments on steadystate CFTR mRNA. Our findings emphasize the importance of: 1) evaluating CFTR mRNA from individual CF compound heterozygotes to assess occurrence of a more highly expressed allele, 2) appropriate selection of assay target position when testing premature termination codons or drugs intended to overcome nonsense-mediated decay, and 3) the need for future and detailed studies of CFTR mRNA regulation, allelic preference, utilization, and steady-state expression as contributors to variable CF clinical phenotype.
  • ||||||||||  Kalydeco (ivacaftor) / Vertex, lumacaftor (VX-809) / Vertex
    GENE EDITING OF W1282X CFTR ONTO A NATIVE GENETIC BACKGROUND, AND IMPLICATIONS FOR IONOCYTE-DEPENDENT TRANSEPITHELIAL TRANSPORT (202) -  Nov 11, 2019 - Abstract #NACFC2019NACFC_17;    
    In summary, the new W1282X cell model should be useful in a number of research contexts (eg, nonsense codon readthrough/drug discovery, gene transfer to polarized respiratory epithelium devoid of CFTR, W1282X CFTR folding/expression on an epithelial (glandular) background, etc). We plan to generate additional PTC, splice defect, and other CFTR variants based on this Calu3 prototype and provide these to the CF research community.
  • ||||||||||  lumacaftor (VX-809) / Vertex
    PROTEOSTASIS PROFILING OF CLASS II CFTR MUTATIONS AS A MECHANISM FOR PREDICTING LUMACAFTOR THERATYPE () -  Nov 11, 2019 - Abstract #NACFC2019NACFC_13;    
    The new technology can be applied to a range of mutations and treatments targeting discrete features of proteostasis. Such methods are designed to identify underlying factors that help explain failure for certain CFTR variants and suggest new protein targets suitable for highthroughput compound library screening.
  • ||||||||||  Symdeko (tezacaftor/ivacaftor) / Vertex, PTI-428 / Proteostasis
    INITIAL RESULTS EVALUATING THE FIRST-IN-CLASS CFTR AMPLIFIER, PTI-428, IN SUBJECTS WITH CF ON BACKGROUND TREATMENT WITH TEZACAFTOR/ IVACAFTOR () -  Nov 11, 2019 - Abstract #NACFC2019NACFC_7;    
    Treatment with PTI-428 led to an increase in CFTR protein production of approximately 50% in subjects with CF on background treatment with tezacaftor/ivacaftor, similar to that seen with PTI-428 plus lumacaftor/ivacaftor. Subject selection may explain the differential impact of PTI-428 on ppFEV1 on backgrounds of lumacaftor/ivacaftor versus tezacaftor/ivacaftor, and thus provides an important example of possible selection bias in the current era of the availability of multiple CFTR modulators.
  • ||||||||||  Kalydeco (ivacaftor) / Vertex, lumacaftor (VX-809) / Vertex, Orkambi (lumacaftor/ivacaftor) / Vertex
    Journal:  Residual function of cystic fibrosis mutants predicts response to small molecule CFTR modulators. (Pubmed Central) -  Nov 6, 2019   
    Together, these variants represent 87% of individuals in the CFTR2 database with at least 1 missense variant. Thus, our results indicate that most individuals with CF carrying missense variants are (a) likely to respond modestly to currently available modulator therapy, while a small fraction will have pronounced responses, and (b) likely to derive the greatest benefit from combination therapy.
  • ||||||||||  Kalydeco (ivacaftor) / Vertex, lumacaftor (VX-809) / Vertex, Orkambi (lumacaftor/ivacaftor) / Vertex
    Journal:  Prolonged co-treatment with HGF sustains epithelial integrity and improves pharmacological rescue of Phe508del-CFTR. (Pubmed Central) -  Nov 6, 2019   
    This was observed in epithelium-like monolayers from both lung and intestinal origin, representing the two systems most affected by adverse symptoms in patients treated with VX-809 or the VX-809/VX-770 combination. Taken together, our findings strongly suggest that co-administration of HGF with corrector/potentiator drugs could be beneficial for CF patients.
  • ||||||||||  lumacaftor (VX-809) / Vertex, Orkambi (lumacaftor/ivacaftor) / Vertex
    Journal:  Compassionate Use of Lumacaftor/Ivacaftor in Cystic Fibrosis: Spanish Experience. (Pubmed Central) -  Oct 27, 2019   
    Taken together, our findings strongly suggest that co-administration of HGF with corrector/potentiator drugs could be beneficial for CF patients. While treatment with lumacaftor/ivacaftor resulted in an improvement in the number of pulmonary severe exacerbations, no improvement in ppFEV1 or BMI was found.