Switching from the originator ivacaftor + tezacaftor + elexacaftor and ivacaftor to a generic formulation in children with cystic fibrosis: a genotype-based analysis of efficacy and safety
Sergienko D.F., Golubtsova O.I., Enina E.A.
Background: Cystic fibrosis (CF) is a systemic monogenic disease caused by mutations in the CFTR gene, leading to chloride channel dysfunction. The advent of CFTR modulators has radically changed the prognosis of the disease, providing significant improvements in clinical outcomes in patients with various CFTR genotypes. However, data on the impact of switching from the originator ivacaftor/tezacaftor/elexacaftor and ivacaftor to a generic version under a single international nonproprietary name in children with cystic fibrosis, taking into account genotypic characteristics, are limited.
Objective: Identification of genotype-associated characteristics of the efficacy and safety of switching from the original targeted triple-drug ivacaftor/tezacaftor/elexacaftor and ivacaftor to its generic version under a single international nonproprietary name in children with cystic fibrosis in routine clinical practice.
Materials and methods: The study included 28 children with a confirmed diagnosis of cystic fibrosis who had previously received the original triple CFTR modulator. After switching to the generic version, patients were followed for 180 days. Four genotypic groups were identified: F508del/F508del (n=6), E92K/E92K (n=4), F508del/E92K (n=8), and E92K/other (n=10). Changes in body mass index (BMI), FEV₁, and FVC (as % of predicted values), as well as sweat chloride levels, were assessed.
Results: In the F508del/F508del group, the median BMI increased by 0.30 kg/m², and the FVC increased by 3.5% of the predicted value. The greatest increase in FVC was observed in patients with the E92K/E92K genotype (+5.0%). Sweat chloride levels remained stable in all groups; no return to positive sweat test values was recorded. The safety profile was comparable across all genotypic subgroups.
Conclusion: Switching from the originator ivacaftor/tezacaftor/elexacaftor and ivacaftor to a generic analogue in children with cystic fibrosis maintains clinical efficacy and safety regardless of the CFTR genotype. The structure of mutations (F508del/F508del, E92K/E92K, F508del/E92K, E92K/others) does not significantly affect the therapeutic response or tolerability of treatment with the generic drug.
For citations: Sergienko D.F., Golubtsova O.I., Enina E.A. Switching from the originator ivacaftor + tezacaftor + elexacaftor and ivacaftor to a generic formulation in children with cystic fibrosis: a genotype-based analysis of efficacy and safety. Pharmateca. 2026;33(3):99-105. (In Russ.). DOI: https://dx.doi.org/10.18565/pharmateca.2026.3.99-105
Authors’ contribution: O.I. Golubtsova – study concept and design. E.A. Enina – data collection and processing. D.F. Sergienko – data analysis, writing the text.
Conflicts of interest: The authors confirm that they have no conflicts of interest to declare.
Funding: The study was not supported by any special grants, subsidies, or other targeted sources. All activities were conducted as part of the routine clinical practice of the centers.
Ethical Approval: The study was approved by the Local Ethics Committee of the State Budgetary Institution “Republican Children’s Clinical Hospital” of the Ministry of Health of Chuvashia, conclusion No. 1 dated February 12, 2026.
Patient Consent for Publication: All patients provided informed consent for the publication of their data.
Authors’ Data Sharing Statement: The data supporting the findings of this study are available upon request from the corresponding author after approval from the principal investigator.
Keywords
cystic fibrosis
CFTR modulators
ivacaftor/tezacaftor/elexacaftor and ivacaftor
CFTR genotype
F508del
E92K
children
generic
therapy switch
About the Authors
Diana F. Sergienko, Dr. Sci. (Med.), Professor, Professor at the Department of Faculty Pediatrics, Astrakhan State Medical University, Astrakhan, Russia; gazken@rambler.ru, ORCID: https://orcid.org/0000-0002-0875-6780 (corresponding author)Olga I. Golubtsova, Cand. Sci. (Med.), Head of the Pulmonology and Allergology Department, Republican Children’s Clinical Hospital, Cheboksary, Russia; vakcina2007@mail.ru, ORCID: https://orcid.org/0000-0002-0875-6780
Elena A. Enina, Cand. Sci. (Med.), Associate Professor, Department of Hospital Pediatrics, Stavropol State Medical University, Stavropol, Russia; Pulmonolog26@yandex.ru, ORCID: https://orcid.org/0000-0002-5306-8223
Similar Articles
