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Kazani S, Rowlands DJ, Bottoli I, et al. Safety and efficacy of the cystic fibrosis transmembrane conductance regulator potentiator icenticaftor (QBW251). J Cyst Fibros. 2020;20(2):250-256doi: 10.1016/j.jcf.2020.11.002.
Kazani, S., Rowlands, D. J., Bottoli, I., Milojevic, J., Alcantara, J., Jones, I., Kulmatycki, K., Machineni, S., Mostovy, L., Nicholls, I., Nick, J. A., Rowe, S. M., Simmonds, N. J., Vegesna, R., Verheijen, J., Danahay, H., Gosling, M., Ayalavajjala, P. S., Salman, M., & Strieter, R. (2021). Safety and efficacy of the cystic fibrosis transmembrane conductance regulator potentiator icenticaftor (QBW251). Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 20(2), 250-256. https://doi.org/10.1016/j.jcf.2020.11.002
Kazani, Shamsah, et al. "Safety and efficacy of the cystic fibrosis transmembrane conductance regulator potentiator icenticaftor (QBW251)." Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society vol. 20,2 (2021): 250-256. doi: https://doi.org/10.1016/j.jcf.2020.11.002
Kazani S, Rowlands DJ, Bottoli I, Milojevic J, Alcantara J, Jones I, Kulmatycki K, Machineni S, Mostovy L, Nicholls I, Nick JA, Rowe SM, Simmonds NJ, Vegesna R, Verheijen J, Danahay H, Gosling M, Ayalavajjala PS, Salman M, Strieter R. Safety and efficacy of the cystic fibrosis transmembrane conductance regulator potentiator icenticaftor (QBW251). J Cyst Fibros. 2021 Mar;20(2):250-256. doi: 10.1016/j.jcf.2020.11.002. Epub 2020 Dec 06. PMID: 33293212.
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J Cyst Fibros. 2021 Mar;20(2):250-256. doi: 10.1016/j.jcf.2020.11.002. Epub 2020 Dec 06.

Safety and efficacy of the cystic fibrosis transmembrane conductance regulator potentiator icenticaftor (QBW251).

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society

Shamsah Kazani, David J Rowlands, Ivan Bottoli, Julie Milojevic, Jose Alcantara, Ieuan Jones, Kenneth Kulmatycki, Surendra Machineni, Lidia Mostovy, Ian Nicholls, Jerry A Nick, Steven M Rowe, Nicholas J Simmonds, Raju Vegesna, Jeroen Verheijen, Henry Danahay, Martin Gosling, Phaninatha Sarma Ayalavajjala, Mohammed Salman, Robert Strieter

Affiliations

  1. Novartis Institutes for BioMedical Research, Cambridge, MA, United States; Novartis Institutes for BioMedical Research, Basel, Switzerland.
  2. Novartis Pharma AG, Basel, Switzerland. Electronic address: [email protected].
  3. Novartis Institutes for BioMedical Research, Basel, Switzerland.
  4. Novartis Healthcare Private Limited, Hyderabad, India.
  5. National Jewish Health, Denver, CO, United States.
  6. University of Alabama at Birmingham, Birmingham, AL, United States.
  7. Adult Cystic Fibrosis Centre, Royal Brompton Hospital and Imperial College, London, United Kingdom.
  8. Novartis Pharmaceuticals corporation, East Hanover, NJ, United States.
  9. Enterprise Therapeutics, Brighton, United Kingdom.
  10. Novartis Pharmaceuticals corporation, East Hanover, NJ, United States; Enterprise Therapeutics, Brighton, United Kingdom; Sussex Drug Discovery Centre, University of Sussex, Brighton, United Kingdom.

PMID: 33293212 DOI: 10.1016/j.jcf.2020.11.002

Abstract

BACKGROUND: This is the first-in-human study of icenticaftor, an oral potentiator of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) channel. Restoration of CFTR activity has shown significant clinical benefits, but more studies are needed to address all CFTR mutations.

METHODS: Safety, pharmacodynamics/pharmacokinetics of icenticaftor were evaluated in a randomized, double-blind, placebo-controlled study in healthy volunteers. Efficacy was assessed in adult CF patients with ≥1 pre-specified CFTR Class III or IV mutation (150 and 450 mg bid), or homozygous for F508del mutation (450 mg bid). Primary efficacy endpoint was change from baseline in lung clearance index (LCI

RESULTS: Class IV mutations were present in 22 patients, Class III in 2 (both S549N), and 25 were homozygous for F508del. Icenticaftor was well-tolerated in healthy and CF subjects with no unexpected events or discontinuations in the CF groups. The most frequent study-drug related adverse events in CF patients were nausea (12.2%), headache (10.2%), and fatigue (6.1%). Icenticaftor 450 mg bid for 14 days showed significant improvements in all endpoints versus placebo in patients with Class III and IV mutations; mean %predicted FEV

CONCLUSIONS: Icenticaftor was safe and well-tolerated in healthy volunteers and CF patients, and demonstrated clinically meaningful changes in lung function and sweat chloride level in CF patients with Class III and IV CFTR mutations. ClinicalTrials.gov: NCT02190604.

Copyright © 2020. Published by Elsevier B.V.

Keywords: Cystic fibrosis; Cystic fibrosis questionnaire; Homozygous F508del mutation; Icenticaftor; Lung clearance index

Conflict of interest statement

Declaration of Competing Interest IB, JM, BS, DR, IJ, KK, SM, LM, IMN, RV, JV, PSA, MSI are employees of Novartis. SK, JA, HD, MG and RS are past employees of Novartis. SMR reports grants, personal fe

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