Elexacaftor-tezacaftor-ivacaftor: The new paradigm to treat people with cystic fibrosis with at least one p.Phe508del mutation

Abstract

Cystic fibrosis is the most common life-limiting genetic disease in the Caucasian population, with median predicted survival progressively improving up to 50 years, thanks to highly standardized multidisciplinary approach. Patients with p.Phe508del homozygosity usually have poorer lung function and higher mortality rates per year than other groups. By reason of that, this population has been among the most eligible target of the cystic fibrosis transmembrane conductance regulator (CFTR) modulators, a new class of drugs that can partially restore CFTR function by the correction of CFTR misfolding and trafficking to the cell surface. This narrative review summarizes the current preclinical and clinical evidence of the triple combination of elexacaftor-tezacaftor-ivacaftor, the new benchmark among highly effective CFTR modulators. It provides details on the efficacy and safety that led to drug regulation and approval and discusses future developments in clinical and translational research.

Keywords: CFTR modulators; Clinical efficacy; Cystic fibrosis; Elexacaftor; Safety; Triple therapy.