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Cystic fibrosis (CF) is an autosomal recessive disorder that predominantly affects individuals of Northern European descent, occurring at a rate of 1 in 3500. It is caused by a genetic mutation in a gene on chromosome 7, most commonly the ΔF508 mutation, that codes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This results in thicker mucus secretions and obstruction pathologies in multiple organs, including the lungs and sinuses.
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Related Experiment Video

Updated: May 21, 2025

Forskolin-induced Swelling in Intestinal Organoids: An In Vitro Assay for Assessing Drug Response in Cystic Fibrosis Patients
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Comparative Efficacy of CFTR Modulators: A Network Meta-analysis.

Imran Hasan Iftikhar1,2, Saad T Rao3, Rufai Nadama4

  • 1Department of Medicine, Division of Pulmonary, Allergy, Critical Care & Sleep Medicine, Emory University School of Medicine, 613 Michael St, NE, Atlanta, GA, USA. imran.hasan.iftikhar@emory.edu.

Lung
|March 19, 2025
PubMed
Summary

Vanzacaftor-tezacaftor-deutivacaftor (VTD) and elexacaftor-tezacaftor-ivacaftor (ETI) demonstrate superior efficacy in improving lung function and quality of life for cystic fibrosis patients compared to older CFTR modulators.

Keywords:
Elexacaftor–tezacaftor–ivacaftorLumacaftor–ivacaftorNetwork meta-analysisTezacaftor–ivacaftorVanzacaftor–tezacaftor–deutivacaftor

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Area of Science:

  • Pharmacology and Therapeutics
  • Pulmonology
  • Genetics

Background:

  • Cystic fibrosis (CF) is a genetic disorder affecting multiple organs, primarily the lungs.
  • Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators are a class of drugs designed to treat the underlying cause of CF.
  • The F508del mutation is the most common CFTR mutation, affecting a large proportion of people with CF (pwCF).

Purpose of the Study:

  • To conduct a comparative efficacy analysis of novel CFTR modulators: vanzacaftor-tezacaftor-deutivacaftor (VTD) and elexacaftor-tezacaftor-ivacaftor (ETI).
  • To compare VTD and ETI against older modulators, tezacaftor-ivacaftor (Tez-Iva) and lumacaftor-ivacaftor (Lum-Iva).
  • To evaluate these modulators in pwCF aged 12 years and older with at least one F508del-CFTR allele.

Main Methods:

  • A network meta-analysis was performed using data from randomized controlled trials and randomized active comparator trials.
  • Frequentist methods were employed to compare drug efficacies and rank them using P-scores.
  • Key outcomes included changes in ppFEV1, CFQ-R scores, SwCl levels, and odds of serious adverse events (SAEs).

Main Results:

  • VTD and ETI showed significantly greater improvements in ppFEV1 and CFQ-R scores compared to Tez-Iva and Lum-Iva.
  • A statistically significant difference in sweat chloride reduction was observed between VTD and ETI, favoring VTD.
  • No significant increase in SAEs was found for any modulator; VTD, ETI, and Tez-Iva showed the lowest association with SAEs.

Conclusions:

  • VTD and ETI are more efficacious than Tez-Iva and Lum-Iva in pwCF carrying at least one F508del-CFTR allele.
  • The findings support the use of VTD and ETI as advanced treatment options for this patient population.
  • VTD and ETI represent a significant advancement in CFTR modulator therapy.