Triple combination ivacaftor + tezacaftor + elexacaftor and ivacaftor for cystic fibrosis: clinical efficacy and safety of the original drug and its generic analogue Trilexa®

Abstract

Triple CFTR modulator therapy with ivacaftor + tezacaftor + elexacaftor and ivacaftor (ITE) has substantially changed the clinical course and prognosis of cystic fibrosis. The expanding use of the bioequivalent generic Trilexa® highlights the need to summarize evidence on its clinical efficacy and safety, including outcomes after switching from the originator Trikafta®. The aim of this study was to summarize and systematize national and international data on the efficacy and safety of triple CFTR modulator therapy with ITE, including the experience of using the original drug and the generic drug, in children and adults with cystic fibrosis. Results. The triple ITE combination is the most widely studied and the most effective of the available methods of pathogenetic therapy for cystic fibrosis. In randomized clinical trials and observational programs, the originator provides an increase in FEV 1, a marked reduction in sweat chloride concentration, improvement in nutritional status, and a significant decrease in the rate of pulmonary exacerbations. Bioequivalence of the generic drug has been confirmed. Russian multicenter and regional studies convincingly show that switching from the originator to bioequivalent generic is accompanied by maintenance of FEV1, FVC, nutritional status, and surrogate markers of CFTR function, while preserving a favorable safety profile. The accumulated clinical experience includes the first documented case of a successfully completed pregnancy and delivery under treatment with a generic ITE regimen. Data from studies evaluating the efficacy and safety of deutivacaftor + tezacaftor + vanzacaftor as a new option for triple CFTR modulator therapy were additionally reviewed. Conclusion. The body of evidence from international randomized clinical trials, registry studies, and Russian regional experience indicates clinical comparability between the originator and bioequivalent generic when switching from one to another. The use of a bioequivalent generic is a justified strategy to improve the availability of pathogenetic treatment with the goal to expand access to targeted therapy.