The new triple CFTR modulator vanzacaftor/tezacaftor/ deutivacaftor (Aliftrek^®) and its place in the treatment of cystic fibrosis

Cystic fibrosis (CF) is a progressive, life-limiting, autosomal recessive monogenic disease caused by mutations in the CFTR gene, leading to dysfunction of chloride channels in epithelial cells of almost all human exocrine systems, disrupting the function of sweat and salivary glands, the exocrine part of the pancreas, the hepatobiliary and reproductive systems, the intestines, and the respiratory tract. The development of CFTR modulators has revolutionized the treatment of CF by correcting CFTR protein dysfunction at the cellular level.

The aim. In our review, we tried to answer the question of whether the new three-component modulator vanzacaftor/tezacaftor/deutivacaftor (VTD) represents a significant step forward in the treatment of people with CF and whether all susceptible patients should switch from elexacaftor/tezaftor/ivacaftor (ETI) to VTD.

Methods. We analyzed all available scientific literature on the comparative efficacy of VTD and ETI. The search was conducted in the PubMed, Scopus, and Web of Science databases.

Results. It has been found that to date (October 2025) there is no proven clinical superiority of VTD over ETI. The drugs are comparable in terms of improving lung function, the number of exacerbations of the bronchopulmonary process, and the number of adverse reactions. Based on sweat test results, VTD demonstrates an advantage in restoring CFTR protein function, indicating the potential for early restoration of normal chloride channel function and prevention of the development or progression of cystic fibrosis, which still needs to be confirmed in real-world clinical practice. The once-daily dosing regimen of VTD could be considered a desirable feature of the drug, but its high cost does not provide ethical arguments in favor of a mass switch from ETI to VTD for the public health benefit. VTD can be prescribed to patients aged 6 years and older who have at least one of 31 additional pathogenic variants not listed in the prescribing information for ETI.

Conclusion. The advisability of discontinuing successful pathogenetic treatment with ETI and prescribing VTD requires further study in real clinical practice.

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