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.

KEYWORDS:

• Cystic fibrosis
• tezacaftor
• CFTR

Declaration of interest

M Jain is a consultant for Vertex and Proteostasis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have received grants and honoraria from Vertex Pharmaceuticals, as well as payment from Proteostasis for being part of an advisory board. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose. Vertex Pharmaceuticals Incorporated provided a scientific accuracy review at the request of the journal editor.

Additional information

Funding

This paper was not funded.