Tenofovir alafenamide

Tenofovir alafenamide, sold under the brand name Vemlidy, is a hepatitis B virus (HBV) nucleotide reverse transcriptase inhibitor medication for the treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disease.[4] It is taken by mouth.[4]

Tenofovir alafenamide
Clinical data
Pronunciation/ˌtəˈnoʊfəvɪər ˌæləˈfɛnəmaɪd/
Trade namesVemlidy
Genvoya (with elvitegravir, cobicistat and emtricitabine)
Odefsey (with emtricitabine and rilpivirine)
Descovy (with emtricitabine)
Symtuza (with darunavir, cobicistat, and emtricitabine)
Other namesGS-7340
AHFS/Drugs.comMonograph
License data
Pregnancy
category
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding~80%[4]
Elimination half-life0.51 hour
ExcretionFeces (31.7%), urine (<1%)
Identifiers
IUPAC name
  • Isopropyl (2S)-2-[[[(1R)-2-(6-aminopurin-9-yl)-1-methyl-ethoxy]methyl-phenoxy-phosphoryl]amino]propanoate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC21H29N6O5P
Molar mass476.474 g·mol−1
3D model (JSmol)
SMILES
  • C[C@H](CN1C=NC2=C(N=CN=C21)N)OC[P@@](=O)(N[C@@H](C)C(=O)OC(C)C)OC3=CC=CC=C3
InChI
  • InChI=1S/C21H29N6O5P/c1-14(2)31-21(28)16(4)26-33(29,32-17-8-6-5-7-9-17)13-30-15(3)10-27-12-25-18-19(22)23-11-24-20(18)27/h5-9,11-12,14-16H,10,13H2,1-4H3,(H,26,29)(H2,22,23,24)/t15-,16+,33+/m1/s1
  • Key:LDEKQSIMHVQZJK-CAQYMETFSA-N
Tenofovir alafenamide fumarate, the salt used in drug formulations

Tenofovir alafenamide is a prodrug of tenofovir. It was developed by Gilead Sciences based on the protide technology of Chris McGuigan for use in the treatment of HIV/AIDS and chronic hepatitis B, and is applied in the form of tenofovir alafenamide fumarate (TAF). Closely related to the commonly used reverse-transcriptase inhibitor tenofovir disoproxil fumarate (TDF), TAF has greater antiviral activity and better distribution into lymphoid tissues than that agent.[6][7] Vemlidy was approved by the U.S. Food and Drug Administration (FDA) in November 2016.[8]

Fixed-dose combinations containing tenofovir alafenamide

Research

Gilead announced a Phase III clinical trial evaluating a single-tablet regimen combining tenofovir alafenamide with cobicistat, emtricitabine and elvitegravir[35] and developed a coformulation of the drug with cobicistat, emtricitabine and the protease inhibitor darunavir.[36][37][38] In a 48-week study comparing elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil (Stribild) to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (Genvoya), the results showed the newer drug's effects to be non-inferior to the established agent, but at much lower dosages and with lower incidence of adverse side effects such as impaired kidney function.[39][40][41] The FDA approved the TAF-based treatment regimen for treatment of HIV-1 in November 2015.[42] Genvoya is the first TAF-based regimen to receive approval.[42]

References
  1. "Tenofovir alafenamide (Vemlidy) Use During Pregnancy". Drugs.com. 26 December 2018. Archived from the original on 9 July 2021. Retrieved 18 April 2020.
  2. "Product Monograph: Vemlidy (tenofovir alafenamide) tablets" (PDF). Government of Canada: The Drug and Health Product Register. 20 August 2020. Archived (PDF) from the original on 10 June 2022. Retrieved 7 June 2022.
  3. "Vemlidy 25 mg film coated tablets - Summary of Product Characteristics (SmPC)". (emc). 8 September 2020. Archived from the original on 11 July 2021. Retrieved 12 November 2020.
  4. "Vemlidy- tenofovir alafenamide tablet". DailyMed. 11 February 2020. Archived from the original on 9 July 2021. Retrieved 18 April 2020.
  5. "Vemlidy EPAR". European Medicines Agency (EMA). Archived from the original on 13 July 2021. Retrieved 12 November 2020.
  6. Eisenberg EJ, He GX, Lee WA (2001). "Metabolism of GS-7340, a novel phenyl monophosphoramidate intracellular prodrug of PMPA, in blood". Nucleosides Nucleotides Nucleic Acids. 20 (4–7): 1091–8. doi:10.1081/NCN-100002496. PMID 11562963. S2CID 24652157.
  7. M Markowitz, A Zolopa, et al. GS-7340 Demonstrates Greater Declines in HIV-1 RNA than Tenofovir Disoproxil Fumarate During 14 Days of Monotherapy in HIV-1 Infected Subjects Archived 25 April 2012 at the Wayback Machine. 18th Conference on Retroviruses and Opportunistic Infections 2 Mar 2011. Paper # 152LB
  8. "FDA Approves Vemlidy (tenofovir alafenamide) for Chronic Hepatitis B in Adults". United States Department of Health and Human Services. 21 November 2016. Archived from the original on 11 October 2019. Retrieved 11 October 2019.
  9. "Genvoya- elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide tablet". DailyMed. 11 February 2019. Archived from the original on 1 August 2020. Retrieved 18 April 2020.
  10. "Genvoya (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide) fixed-dose combination tablet". U.S. Food and Drug Administration (FDA). 8 December 2015. Archived from the original on 29 July 2020. Retrieved 28 July 2020.
  11. "Summary Review: Genvoya" (PDF). US Food and Drug Administration. 6 August 2012. Archived (PDF) from the original on 29 July 2020. Retrieved 29 July 2020.
  12. "Genvoya EPAR". European Medicines Agency (EMA). Archived from the original on 8 August 2020. Retrieved 28 July 2020.
  13. "Drug Approval Package: Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate) Fixed Dose". U.S. Food and Drug Administration (FDA). 10 October 2012. Archived from the original on 29 July 2020. Retrieved 28 July 2020.
  14. "Summary Review: Stribild" (PDF). US Food and Drug Administration. 19 October 2015. Archived (PDF) from the original on 29 July 2020. Retrieved 29 July 2020.
  15. "Stribild- elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate tablet, film coated". DailyMed. 28 January 2019. Archived from the original on 29 July 2020. Retrieved 28 July 2020.
  16. "Stribild EPAR". European Medicines Agency (EMA). Archived from the original on 29 July 2020. Retrieved 28 July 2020.
  17. "Odefsey- emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide tablet". DailyMed. 6 December 2019. Archived from the original on 1 August 2020. Retrieved 18 April 2020.
  18. "Odefsey (emtricitabine, rilpivirine, and tenofovir alafenamide) Tablets". U.S. Food and Drug Administration (FDA). 29 November 2016. Archived from the original on 13 April 2021. Retrieved 28 July 2020.
  19. "Odefsey EPAR". European Medicines Agency (EMA). Archived from the original on 29 July 2020. Retrieved 28 July 2020.
  20. "Drug Approval Package: (emtricitabine/rilpivirine/tenofovir disoproxil fumarate) NDA #202123". U.S. Food and Drug Administration (FDA). 6 September 2012. Archived from the original on 29 July 2020. Retrieved 28 July 2020.
  21. "Summary Review: Complera" (PDF). US Food and Drug Administration. 19 July 2011. Archived (PDF) from the original on 1 April 2021. Retrieved 29 July 2020.
  22. "Complera- emtricitabine, rilpivirine hydrochloride, and tenofovir disoproxil fumarate tablet, film coated". DailyMed. 9 December 2019. Archived from the original on 29 July 2020. Retrieved 28 July 2020.
  23. "Descovy- emtricitabine and tenofovir alafenamide tablet". DailyMed. 13 January 2020. Archived from the original on 24 June 2021. Retrieved 18 April 2020.
  24. "FDA approves second drug to prevent HIV infection as part of ongoing efforts to end the HIV epidemic". U.S. Food and Drug Administration (FDA). 3 October 2019. Archived from the original on 11 October 2019. Retrieved 11 October 2019.
  25. Mandavilli, Apoorva (4 October 2019). "F.D.A. Approves New H.I.V.-Prevention Drug, but Not for Everyone". The New York Times. Archived from the original on 9 July 2021. Retrieved 11 October 2019.
  26. "Biktarvy- bictegravir sodium, emtricitabine, and tenofovir alafenamide fumarate tablet". DailyMed. 8 August 2019. Archived from the original on 1 August 2020. Retrieved 18 April 2020.
  27. "Symtuza- darunavir, cobicistat, emtricitabine, and tenofovir alafenamide tablet, film coated". DailyMed. 6 March 2020. Archived from the original on 9 July 2021. Retrieved 18 April 2020.
  28. "Drug Approval Package: Symtuza (darunavir, cobicistat, emtricitabine, and tenofovir alafenamide)". U.S. Food and Drug Administration (FDA). 11 December 2018. Archived from the original on 9 July 2021. Retrieved 19 August 2020.
  29. "Symtuza EPAR". European Medicines Agency. Archived from the original on 10 July 2021. Retrieved 19 August 2020.
  30. "TGA eBS - Product and Consumer Medicine Information Licence". Archived from the original on 20 February 2022. Retrieved 20 February 2022.
  31. "Symtuza 800/150/200/10 Tablets". NPS MedicineWise. 15 July 2021. Archived from the original on 20 February 2022. Retrieved 19 February 2022.
  32. "Drugs@FDA: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Archived from the original on 9 July 2021. Retrieved 5 December 2020.
  33. "Drugs@FDA: FDA-Approved Drugs". accessdata.fda.gov. Archived from the original on 2 April 2022. Retrieved 2 April 2022.
  34. "Tentative Approval: Dolutegravir, Lamivudine, and Tenofovir Alafenamide Tablets" (PDF). US Food and Drug Administration. 30 March 2022. Archived (PDF) from the original on 7 May 2022. Retrieved 2 April 2022.
  35. "Gilead Initiates Phase 3 Clinical Program for Tenofovir Alafenamide, a Novel Low-Dose Prodrug for the Treatment of HIV" (Press release). Gilead. 24 January 2013. Archived from the original on 11 October 2019.
  36. "Gilead Sciences Finalizes Agreement with Tibotec Pharmaceuticals to Develop and Commercialize a Single-Tablet Regimen of Prezista with Emtriva, GS 7340 and Cobicistat". Gilead Sciences (Press release). 15 November 2011. Archived from the original on 11 October 2019. Retrieved 10 October 2019.
  37. GS-7340 Packs Greater HIV Punch, Potentially Better Safety, Versus Viread Archived 8 September 2015 at the Wayback Machine Horn, Tim. 15 Mar 2012. AIDSmeds.com
  38. Pharmacokinetics of a Novel EVG/COBI/FTC/GS-7340 Single Tablet Regimen Archived 28 November 2020 at the Wayback Machine. 13th International Workshop on Clinical Pharmacology of HIV Therapy. Barcelona, Spain. April 16–18, 2012.
  39. Once-Daily Tenofovir Prodrug Combo Pill as Effective as Stribild Archived 20 September 2015 at the Wayback Machine. AIDSmeds.com 1 Nov 2012.
  40. CROI 2013: New Pro-drug Tenofovir Alafenamide Appears Equally Effective but Better Tolerated Archived 25 October 2020 at the Wayback Machine. Highleyman, Liz. HIVandHepatitis.com. 6 March 2013.
  41. Horn, T. et al. Tenefovir Alafenamide Fumarate (TAF) Sign-On Letter to Gilead Archived 19 November 2019 at the Wayback Machine. 13 June 2013. Treatment Action Group.
  42. "U.S. Food and Drug Administration Approves Gilead's Single Tablet Regimen Genvoya (Elvitegravir, Cobicistat, Emtricitabine and Tenofovir Alafenamide) for Treatment of HIV-1 Infection" (Press release). Gilead. 5 November 2015. Archived from the original on 8 November 2015.
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