Chemistry:Tezacaftor

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Tezacaftor is a medication used for the treatment of cystic fibrosis.[1][2] It is available in fixed-dose combination medications.[3][4][5]

The combination of tezacaftor with ivacaftor (brand name Symdeko) was approved for medical use in the United States in February 2018,[6][1] and in Canada in June 2018.[7] As brand name Symkevi it was approved for medical use in the European Union in October 2018.[8]

The combination of tezacaftor with elexacaftor and ivacaftor (brand name Trikafta) was approved for medical use in the United States in October 2019,[9][10][11] and in Canada in June 2021.[12] As brand name Kaftrio it was approved for medical use in the European Union in August 2020.[13]

The combination of tezacaftor with vanzacaftor and deutivacaftor (brand name Alyftrek) was approved for medical use in the United States in December 2024.[14]

Mechanism of action

Tezacaftor acts as a corrector to help the folding and presentation of the CFTR protein to the cell surface, which improves its function for individuals with a F508del mutation.[1][15][16]

Clinical trials

The EVOLVE and EXPAND study findings were published in 2017.[17]

EVOLVE trial

The EVOLVE trial analyzed tezacaftor/ivacaftor in participants with cystic fibrosis, specifically with the homozygous for Phe508del mutation.[18] The EVOLVE trial is a phase 3, double-blinded, multicenter, randomized, placebo-controlled, parallel-group trial, that was which evaluated therapy with a combination of tezacaftor and ivacaftor in participants that are aged 12 years of age and older.[18]

510 participants were randomized and 509 participants were given either 100 mg of tezacaftor once daily and 150 mg of ivacaftor twice daily or a placebo for 24 weeks.[18] The combination of drugs was efficacious in participants who had cystic fibrosis with the Phe508del mutation and the adverse effects in both treatment groups were similar.[18]

History

The US Food and Drug Administration (FDA) granted the application for tezacaftor and ivacaftor combination therapy orphan drug and priority review designations, and granted the approval of Symdeko to Vertex Pharmaceuticals.[2][19] The European Medicines Agency (EMA) designated the combination an orphan medicine.[8]

The FDA and the EMA granted the application for elexacaftor, tezacaftor, and ivacaftor combination therapy an orphan drug designation.[20][13][21]

The FDA granted the application for vanzacaftor, tezacaftor, and deutivacaftor combination therapy an orphan drug designation.[22]

Society and culture

Names

Tezacaftor is the international nonproprietary name.[23]

References

  1. ↑ 1.0 1.1 1.2 "Drug Trials Snapshots: Symdeko". 7 March 2018. https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-symdeko.  Public Domain This article incorporates text from this source, which is in the public domain.
  2. ↑ 2.0 2.1 "FDA expands approval of treatment for cystic fibrosis to include patients ages 6 and older". U.S. Food and Drug Administration (FDA) (Press release). 21 June 2019. Archived from the original on 21 November 2019. Retrieved 20 November 2019. Public Domain This article incorporates text from this source, which is in the public domain.
  3. ↑ "The combination of tezacaftor and ivacaftor in the treatment of patients with cystic fibrosis: clinical evidence and future prospects in cystic fibrosis therapy". Therapeutic Advances in Respiratory Disease 13. 2019. doi:10.1177/1753466619844424. PMID 31027466. 
  4. ↑ "Tezacaftor and ivacaftor for the treatment of cystic fibrosis". Expert Review of Respiratory Medicine 14 (1): 15–30. January 2020. doi:10.1080/17476348.2020.1682998. PMID 31626570. https://www.research.manchester.ac.uk/portal/en/publications/tezacaftor-and-ivacaftor-for-the-treatment-of-cystic-fibrosis(a60081ad-608e-43a3-8e4e-06fe89de284f).html. 
  5. ↑ "The preclinical discovery and development of the combination of ivacaftor + tezacaftor used to treat cystic fibrosis". Expert Opinion on Drug Discovery 15 (8): 873–891. August 2020. doi:10.1080/17460441.2020.1750592. PMID 32290721. 
  6. ↑ "Symdeko- tezacaftor and ivacaftor kit". 9 February 2024. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=302ae804-37db-44fd-ac2f-3dbdeda9aa4b. 
  7. ↑ "Symdeko Product information". https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=96881. 
  8. ↑ 8.0 8.1 "Symkevi EPAR". 27 February 2017. https://www.ema.europa.eu/en/medicines/human/EPAR/symkevi. 
  9. ↑ "Trikafta- elexacaftor, tezacaftor, and ivacaftor kit". 29 January 2020. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f354423a-85c2-41c3-a9db-0f3aee135d8d. 
  10. ↑ "Drug Trials Snapshots: Trikafta". 31 October 2019. https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-trikafta. 
  11. ↑ "FDA approves new breakthrough therapy for cystic fibrosis". U.S. Food and Drug Administration (FDA) (Press release). 21 October 2019. Archived from the original on 13 November 2019. Retrieved 13 November 2019. Public Domain This article incorporates text from this source, which is in the public domain.
  12. ↑ "Trikafta Product information". 22 June 2021. https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=100648. 
  13. ↑ 13.0 13.1 "Kaftrio EPAR". 14 December 2018. https://www.ema.europa.eu/en/medicines/human/EPAR/kaftrio. 
  14. ↑ "Vertex Announces US FDA Approval of Alyftrek, a Once-Daily Next-in-Class CFTR Modulator for the Treatment of Cystic Fibrosis" (Press release). Vertex. 20 December 2024. Retrieved 24 December 2024 – via Business Wire.
  15. ↑ "Tezacaftor (VX-661) for Cystic Fibrosis". Cystic Fibrosis News Today. Pensacola, FL: BioNews Services, LLC. https://cysticfibrosisnewstoday.com/tezacaftor-vx-661-for-cystic-fibrosis. 
  16. ↑ Ridley, Kaden (2020). "Elexacaftor-Tezacaftor-Ivacaftor: The First Triple-Combination Cystic Fibrosis Transmembrane Conductance Regulator Modulating Therapy". The Journal of Pediatric Pharmacology and Therapeutics 25 (3): 192–197. doi:10.5863/1551-6776-25.3.192. PMID 32265602. 
  17. ↑ "FDA Approves New Cystic Fibrosis Drug Combo - Symdeko approved for patients with specific CFTR mutations". MedPage Today, LLC. 13 February 2018. https://www.medpagetoday.com/pulmonology/cysticfibrosis/71125. 
  18. ↑ 18.0 18.1 18.2 18.3 Taylor-Cousar, Jennifer (23 November 2017). "Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del". New England Journal of Medicine 377 (21): 2013–2023. doi:10.1056/NEJMoa1709846. PMID 29099344. 
  19. ↑ "Tezacaftor and Ivacaftor Orphan Drug Designations and Approvals". 15 June 2017. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=577517. 
  20. ↑ "Trikafta Orphan Drug Designations and Approvals". 29 August 2018. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=647618. 
  21. ↑ "EU/3/18/2116 - orphan designation for treatment of cystic fibrosis". 14 December 2018. https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu-3-18-2116. 
  22. ↑ "Alyftrek Orphan Drug Designations and Approvals". https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=777220. 
  23. ↑ "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 76". WHO Drug Information 30 (3). 2016. 



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