Experience with the use of the generic drug ivacaftor + tezacaftor + elexacaftor and ivacaftor in an adult patient with cystic fibrosis in clinical practice

Cystic fibrosis is the most common hereditary clinically and genetically heterogeneous disease with an autosomal recessive type of inheritance, the main cause of which is mutations in the cystic fibrosis transmembrane conduction regulator CFTR gene. An important contribution to the correction of the main cellular defect was the emergence of a new group of drugs, CFTR modulators, small molecules that either correct improper protein folding and processing, or improve the functioning of channels to enhance the apical transport of chlorides and bicarbonates. By partially restoring channel function, CFTR modulators improve a number of clinical parameters, but the effect varies depending on CFTR mutations, modulator combinations used, and individual clinical characteristics. The triple fixed combination of elexacaftor + tezacaftor + ivacaftor has the potential to treat at least 85% of cystic fibrosis patients, highlighting its impact on treatment and prognosis in cystic fibrosis. The presented clinical case describes the experience of including the generic drug ivacaftor + tezacaftor + elexacaftor and ivacaftor in the treatment of an adult patient with late diagnosis of cystic fibrosis. The 6-month therapy resulted in an increase in nutritional status, a decrease in shortness of breath, and an improvement in general condition, laboratory examination, sweat test, gas exchange, and lung function, and did not cause any adverse events. The data obtained coincided with the results of the conducted studies. Further studies are being conducted to better understand the effect of CFTR modulators on other manifestations of cystic fibrosis or the possibility of treating cystic fibrosis patients with rare CFTR mutations using the triple combination ivacaftor + tezacaftor + elexacaftor.

1. Kondratyeva EI, Voronkova AYu, Kashirskaya NYu, Krasovsky SA, Starinova MA, Amelina EL et al. Russian registry of patients with cystic fibrosis: lessons and perspectives. Pulmonologiya. 2023;33(2):171–181. (In Russ.) https://doi.org/10.18093/0869-0189-2023-33-2-171-181.

2. Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023;11(11):CD010966. https://doi.org/10.1002/14651858.CD010966.pub4.

3. Ramsey B, Correll CU, DeMaso DR, McKone E, Tullis E, Taylor-Cousar JL et al. Elexacaftor/Tezacaftor/Ivacaftor Treatment and Depression-related Events. Am J Respir Crit Care Med. 2024;209(3):299–306. https://doi.org/10.1164/rccm.202308-1525OC.

4. Hoy SM. Elexacaftor/Ivacaftor/Tezacaftor: First Approval. Drugs. 2019;79(18):2001–2007. https://doi.org/10.1007/s40265-019-01233-7.

5. Wainwright C, McColley SA, McNally P, Powers M, Ratjen F, Rayment JH et al. Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Children Aged ≥6 Years with Cystic Fibrosis and at Least One F508del Allele: A Phase 3, Open-Label Clinical Trial. Am J Respir Crit Care Med. 2023;208(1):68–78. https://doi.org/10.1164/rccm.202301-0021OC.

6. Kapouni N, Moustaki M, Douros K, Loukou I. Efficacy and Safety of ElexacaftorTezacaftor-Ivacaftor in the Treatment of Cystic Fibrosis: A Systematic Review. Children. 2023;10(3):554. https://doi.org/10.3390/children10030554.

7. Mall MA, Mayer-Hamblett N, Rowe SM. Cystic Fibrosis: Emergence of Highly Effective Targeted Therapeutics and Potential Clinical Implications. Am J Respir Crit Care Med. 2020;201:1193–1208. https://doi.org/10.1164/rccm.201910-1943SO.