Elexacaftor-Tezacaftor-Ivacaftor: The First Triple-Combination Cystic Fibrosis Transmembrane Conductance Regulator Modulating Therapy

Abstract

Elexacaftor-tezacaftor-ivacaftor is a newly approved triple-combination cystic fibrosis transmembrane conductance regulator (CFTR) modulating therapy that contains 2 correctors and a potentiator of the CFTR channel. Its labeled indication for use is for persons 12 years of age and older with at least 1 F508del mutation for the CFTR gene. This drug combination provides potential therapy to many patients who had previously been excluded from CFTR modulation therapy due to the nature of their genetic mutations. The efficacy demonstrated in clinical trials surpasses the currently available therapies related to lung function, quality of life, sweat chloride reduction, and reducing exacerbations. The most common adverse events seen in clinical trials included rash and headache, and laboratory monitoring is recommended to evaluate liver function. Continued evaluation of patient data is needed to confirm its long-term safety and efficacy. Elexacaftor-tezacaftor-ivacaftor is a monumental and encouraging therapy for cystic fibrosis; however, approximately 10% of the CF population are not candidates for this or any other CFTR modulation therapy.

Keywords: CFTR modulator; cystic fibrosis; elexacaftor; ivacaftor; tezacaftor.

Figure.

Classes of CFTR mutations. Class I and II mutations result in CFTR protein that does not reach the cell surface due to impaired protein translation in the cell nucleus (Class I) or misfolded protein in the golgi apparatus (Class II). Class III and IV mutations result in CFTR that reaches the cell surface but exhibits impaired function due to a gating defect (Class III) or decrease conductivity (Class IV). Class V mutations lead to a reduced production of normal CFTR.