Tezacaftor for the treatment of cystic fibrosis.

Abstract

INTRODUCTION:

Cystic fibrosis (CF) is the most common, life-limiting autosomal recessive disease in Caucasians, and is caused by defects in production of the CFTR ion channel. Until recently, there were no available treatments targeting the disease-causing defects in CFTR but newly developed CFTR modulators are changing the course of disease in CF. The newest modulator, tezacaftor, is a CFTR corrector that was recently approved by the FDA to be used in combination with the first approved CFTR potentiator, ivacaftor. Areas covered: A detailed review of the clinical trials and published literature, focusing on safety and efficacy, leading to the approval of tezacaftor in CF. Expert commentary: Recent trials have demonstrated that the combination of tezacaftor-ivacaftor is a slightly superior combination to its predecessor, lumacaftor-ivacaftor, with respect to an increase in FEV1, adverse event profile, and drug-drug interactions. It is also approved for a large number of non-F508del, residual function mutations that are predicted to respond based on in vitro testing. The horizon for continued improvements in CFTR-targeted treatments is promising, with three-drug combinations currently in Phase 3 clinical trials, and other drugs with novel mechanisms of action being studied. Within the next 5 years, the vast majority of patients with CF are expected to have a modulator approved for their genotype.

• Authors: Marc A Sala, Manu Jain
• Journal: Expert review of respiratory medicine (Expert Rev Respir Med) Vol. 12 Issue 9 Pg. 725-732 (09 2018) ISSN: 1747-6356 [Electronic] England
• PMID: 30073878 (Publication Type: Journal Article, Review)

Chemical References

• Aminophenols
• Aminopyridines
• Benzodioxoles
• Drug Combinations
• Indoles
• Quinolones
• lumacaftor, ivacaftor drug combination
• tezacaftor
• Cystic Fibrosis Transmembrane Conductance Regulator
• ivacaftor

Topics

• Aminophenols (therapeutic use)
• Aminopyridines (therapeutic use)
• Benzodioxoles (therapeutic use)
• Cystic Fibrosis (drug therapy, genetics, physiopathology)
• Cystic Fibrosis Transmembrane Conductance Regulator (genetics)
• Drug Combinations
• Genotype
• Humans
• Indoles (therapeutic use)
• Mutation
• Quinolones (therapeutic use)