Pathogenetic therapy with ivacaftor + tezacaftor + elexacaftor plus ivacaftor: Assessment of efficacy and safety of switching within a single INN in children with cystic fibrosis in the Yaroslavl and Tula regions

Introduction. The triple combination of CFTR modulators (ivacaftor/tezacaftor/elexacaftor plus ivacaftor) is considered a modern and highly effective pathogenetic therapy for cystic fibrosis in patients with CFTR genotypes sensitive to this regimen.
Aim. To assess the efficacy and safety of pathogenetic therapy with a triple fixed-dose combination during a sequential switch from the originator product (Trikafta®) to the generic product (Trilexa®) within the same INN (ivacaftor/tezacaftor/elexacaftor plus ivacaftor) in patients with cystic fibrosis treated in routine clinical practice in the Yaroslavl and Tula regions.
Materials and methods. A retrospective analysis of clinical data from 18 patients with cystic fibrosis living in the Yaroslavl and Tula regions was performed. Outcomes were evaluated at four time points: initiation of Trikafta® therapy, after 12 months of Trikafta®, initiation of Trilexa®, and 12 months after the switch. Sweat chloride concentration, body mass index (BMI), forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and treatment safety were assessed.
Results. Sweat chloride concentration decreased from 107.22 ± 16.27 to 73.39 ± 16.30 mmol/L after one year of Trikafta® therapy, and from 67.28 ± 25.47 to 60.76 ± 13.20 mmol/L after 12 months of Trilexa®. BMI increased from 15.74 ± 1.88 to 17.03 ± 2.07 kg/m² and then to 18.88 ± 2.18 kg/m² with the originator and generic products, respectively. FEV1 rose from 107.11 ± 24.75 to 119.10 ± 21.75% predicted on Trikafta® and to 121.81 ± 21.55% predicted after 12 months of Trilexa®. One transient episode of skin rash was observed during Trikafta® therapy. No adverse events were reported with Trilexa®.
Conclusion. Switching from the originator to the generic triple pathogenetic therapy ivacaftor/tezacaftor/elexacaftor plus ivacaftor was associated with maintenance of the achieved clinical response and a favorable safety profile

1. Авдеев СН, Аветисян ЛР, Амелина ЕЛ, Баранов АА, Баранова ИА, Басова АЯ и др. Клинические рекомендации по кистозному фиброзу (муковисцидозу). 2025. Режим доступа: https://ostrovaru.com/material/klinicheskie-rekomendaczii-po-kistoznomu-fibrozu-mukovisczidozu-2021-g.

2. Southern KW, Castellani C, Lammertyn E, Smythd A, Devanter D, Koningsbruggen-Rietschel S et al. Standards of care for CFTR variant-specific therapy (including modulators) for people with cystic fibrosis. J Cyst Fibros. 2023;22(1):17–30. https://doi.org/10.1016/j.jcf.2022.09.007.

3. Middleton PG, Mall MA, Dřevínek P, Lands LC, McKone EF, Polineni D et al. Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med. 2019;381(19):1809–1819. https://doi.org/10.1056/NEJMoa1908639.

4. Heijerman HGM, McKone EF, Downey DG, Van Braeckel E, Rowe SM, Tullis E et al. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet. 2019;394(10212):1940–1948. https://doi.org/10.1016/S0140-6736(19)32597-8.

5. Lopes K, Custódio C, Lopes C, Bolas R, Azevedo P. Elexacaftor/tezacaftor/ivacaftor-real-world clinical effectiveness and safety. A single-center Portuguese study. J Bras Pneumol. 2023;49(2):e20220312. https://doi.org/10.36416/1806-3756/e20220312.

6. Keens T, Hoffman V, Topuria I, Elder K, Cerf S, Mulder K et al. Real-world effectiveness of elexacaftor/tezacaftor/ivacaftor on the burden of illness in adolescents and adults with cystic fibrosis. Heliyon. 2024;10(7):e28508. https://doi.org/10.1016/j.heliyon.2024.e28508.

7. Kondratyeva EI, Zhekaite EK, Voronkova AYu, Fatkhullina IR, Sherman VD, Shadrina VV, Odinaeva ND. Age-related peculiarities of the efficiency of the CFTR modulator elexacaftor/tezacaftor/ivacaftor in patients with cystic fibrosis. Russian Pediatric Journal. 2025;28(4 Suppl.):40–41. (In Russ.) Available at: https://www.elibrary.ru/aklfgz.

8. Amelina EL, Krasovskiy SA, Shumkova GL, Krylova NA. Тargeted therapy for CF patients with F508del/F508del genotype. Pulmonologiya. 2019;29(2):235–238. (In Russ.) https://doi.org/10.18093/0869-0189-2019-29-2-235-238.

9. Kondratyeva EI, Avdeev SN, Kutsev SI. History of the use of CFTR modulators in the treatment of cystic fibrosis. Journal of Respiratory Medicine. 2025;1(3):40–50. (In Russ.) https://doi.org/10.17116/respmed2025103140.

10. Merzhoeva ZM, Gaynitdinova VV, Avdeev SN. Experience with the use of the generic drug ivacaftor + tezacaftor + elexacaftor and ivacaftor in an adult patient with cystic fibrosis in clinical practice. Meditsinskiy Sovet. 2025;19(9):134–138. (In Russ.) https://doi.org/10.21518/ms2025-129.

11. Kondratyeva EI, Voronkova AYu, Fatkhullina IR, Orlov AV, Pyaterkina OG, Protasova TA, Psyurnikova OS. Study of the efficacy and safety of the generic drug ivacaftor + tezacaftor + elexacaftor/ivacaftor (trade name Trilexa®). Pulmonologiya. 2025;35(6):832–843. (In Russ.) https://doi.org/10.18093/0869-0189-2025-35-6-832-843.

12. Красовский СА, Кагазежев РУ. Применение генерического препарата ETI у пациентов с муковисцидозом. Пульмонология. 2023;33(6):781–791. https://doi.org/10.18093/0869-0189-2023-33-6-781-791.

13. Krasovskiy SA, Kagazezhev RU. Using generic drug elexacaftor/tezacaftor/ivacaftor+ ivacaftor in patients with cystic fidosis in routine clinical practice. Pulmonologiya. 2023;33(6):781–791. (In Russ.) https://doi.org/10.18093/0869-0189-2023-33-6-781-791.

14. Marshalkina TV, Zhanuzakova NT, Mukatova IY, Kim SS, Amelina EL. The First Results of Targeted Therapy in Children with Cystic Fibrosis in Kazakhstan. Nauka i Zdravookhranenie. 2024;26(4):7–14. Available at: https://oldjournal.ssmu.kz/publication/511/2024-4-7-14.

15. Kenzhebayeva YZh, Mukatova IYu, Amelina EA, Rapilbekova GK, Ivanova-Razumova TV., Tuleutaev E.T. Pregnancy and childbirth in a cystic fibrosis patient receiving a generic CFTR modulator: the first clinical case in Republic of Kazakhstan. Pulmonologiya. 2025;35(4):561–567. (In Russ.) https://doi.org/10.18093/0869-0189-2025-35-4-561-567.