Lenacapavir

Last updated

Lenacapavir
Lenacapavir.svg
Clinical data
Trade names Sunlenca
Other namesGS-CA1, GS-6207
License data
Pregnancy
category
Routes of
administration 		By mouth, subcutaneous
Drug class Capsid inhibitors
ATC code
Legal status
Legal status
Identifiers
  • N-[(1S)-1-{3-[4-chloro-3-(methanesulfonamido)-1-(2,2,2- trifluoroethyl)-1H-indazol-7-yl]-6-[3-(methanesulfonyl)-3- methylbut-1-yn-1-yl]pyridin-2-yl}-2-(3,5-difluorophenyl)ethyl]-2- [(3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro- 1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl]acetamide
CAS Number
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
Chemical and physical data
Formula C39H32ClF10N7O5S2
Molar mass 968.28 g·mol−1
3D model (JSmol)
  • CC(C)(C#Cc1ccc(-c2ccc(Cl)c3c(NS(C)(=O)=O)nn(CC(F)(F)F)c23)c([C@H](Cc2cc(F)cc(F)c2)NC(=O)Cn2nc(C(F)(F)F)c3c2C(F)(F)[C@@H]2C[C@H]32)n1)S(C)(=O)=O
  • InChI=1S/C39H32ClF10N7O5S2/c1-36(2,63(3,59)60)10-9-21-5-6-22(23-7-8-26(40)30-32(23)57(17-37(43,44)45)54-35(30)55-64(4,61)62)31(51-21)27(13-18-11-19(41)14-20(42)12-18)52-28(58)16-56-34-29(33(53-56)39(48,49)50)24-15-25(24)38(34,46)47/h5-8,11-12,14,24-25,27H,13,15-17H2,1-4H3,(H,52,58)(H,54,55)/t24-,25+,27-/m0/s1
  • Key:BRYXUCLEHAUSDY-WEWMWRJBSA-N

Lenacapavir, sold under the brand name Sunlenca, is an antiretroviral medication used to treat HIV/AIDS. [9] [10] It is taken by mouth or by subcutaneous injection. [9] [10]

Contents

The most common side effects include reactions at the injection site and nausea. [10] [11]

Lenacapavir was approved for medical treatment in the European Union in August 2022, [10] [12] in Canada in November 2022, [5] [6] and in the United States in December 2022. [9] [11] [13] [14] It is the first of a class of drugs called capsid inhibitors to be approved by the US Food and Drug Administration (FDA) for treating HIV/AIDS. [11] [15]

Medical uses

Lenacapavir, in combination with other antiretrovirals, is indicated for the treatment of HIV/AIDS. [9] It is used in heavily treatment-experienced adults with multiple drug resistance in whom current antiretroviral therapy is ineffective due to resistance, intolerance or safety considerations. [9] [11] . It has also been found to be highly effective as HIV pre-exposure prophylaxis (PrEP) in heterosexual women in Africa. [16] Further studies are ongoing assessing effectiveness in men who have sex with men and people who inject drugs. [17]

Mechanism of action

Lenacapavir works by binding directly to the interface between HIV-1 viral capsid protein (p24) subunits in capsid hexamers, interfering with essential steps of viral replication, including capsid-mediated nuclear uptake of HIV-1 proviral DNA[ clarification needed ], virus assembly and release, production of capsid protein subunits, and capsid core formation. [9] [11] The US Food and Drug Administration considers it to be a first-in-class medication. [15] [18]

History

Lenacapavir was developed by Gilead Sciences. [19]

The safety and efficacy of lenacapavir were established through a multicenter clinical trial with 72 participants whose HIV infections were resistant to multiple classes of HIV medications. [11] These participants had to have high levels of virus in their blood despite being on antiretroviral drugs. [11] Participants were enrolled into one of two study groups. [11] One group was randomized to receive either lenacapavir or placebo in a double-blind fashion, and the other group received open-label lenacapavir. [11] The primary measure of efficacy was the proportion of participants in the randomized study group who achieved a certain level of reduction in virus during the initial 14 days compared to baseline. [11]

The US Food and Drug Administration granted the application for lenacapavir priority review, fast track, and breakthrough therapy designations. [11]

Society and culture

In June 2022, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Sunlenca, intended for the treatment of adults with multidrug‑resistant human immunodeficiency virus type 1 (HIV‑1) infection. [20] The applicant for this medicinal product is Gilead Sciences Ireland UC. [20]

Lenacapavir was approved for medical use in the European Union in August 2022, [10] [21] in Canada in November 2022, [5] [6] and in the United States in December 2022. [11]

Economics

As of 2024 the drug, produced by Gilead, costs US$42,250 for the first year. A study presented in July 2024 [22] found that mass production of a generic version would allow a profit margin of 30% on an annual price of $40 if used by 10 million people. The authors said that lowering HIV levels significantly would probably require 60 million people to take the drug preventatively. [23]

Research

As of 2021, it is in phase II/III clinical trials. [24] It is being investigated as a treatment for HIV patients infected with multidrug-resistant virus and as a twice-yearly injectable for pre-exposure prophylaxis. [24] [25]

Studies have been conducted for the use of lenacapavir in treatment-naive individuals. [26] For virally suppressed individuals switching treatment, early studies have tested lenacapavir injections in combination with infusions of the broadly neutralizing antibodies teropavimab and zinlirvimab [27] as well as lenacapavir with islatravir. [28]

In July 2024, a study reported 100% efficacy for pre-exposure HIV prevention (PrEP). The randomized phase 3 clinical trial involved 5,338 young women in South Africa and Uganda. All 2,134 women who received an injection every six months remained HIV-free. In contrast, groups taking other daily oral PrEP drugs still had HIV cases, likely due to low adherence. [29] [30] [31] [32]

Related Research Articles

<span class="mw-page-title-main">Zidovudine</span> Antiretroviral medication

Zidovudine (ZDV), also known as azidothymidine (AZT), was the first antiretroviral medication used to prevent and treat HIV/AIDS. It is generally recommended for use in combination with other antiretrovirals. It may be used to prevent mother-to-child spread during birth or after a needlestick injury or other potential exposure. It is sold both by itself and together as lamivudine/zidovudine and abacavir/lamivudine/zidovudine. It can be used by mouth or by slow injection into a vein.

<span class="mw-page-title-main">Enfuvirtide</span> Chemical compound

Enfuvirtide (INN), sold under the brand name Fuzeon, is an HIV fusion inhibitor, the first of a class of antiretroviral drugs used in combination therapy for the treatment of AIDS/HIV.

<span class="mw-page-title-main">Atazanavir</span> Chemical compound

Atazanavir, sold under the brand name Reyataz among others, is an antiretroviral medication used to treat HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for prevention after a needlestick injury or other potential exposure. It is taken by mouth.

<span class="mw-page-title-main">Tenofovir disoproxil</span> Antiviral drug used to treat or prevent HIV and hepatitis infections

Tenofovir disoproxil, sold under the brand name Viread among others, is a medication used to treat chronic hepatitis B and to prevent and treat HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for prevention of HIV/AIDS among those at high risk before exposure, and after a needlestick injury or other potential exposure. It is sold both by itself and together in combinations such as emtricitabine/tenofovir, efavirenz/emtricitabine/tenofovir, and elvitegravir/cobicistat/emtricitabine/tenofovir. It does not cure HIV/AIDS or hepatitis B. It is available by mouth as a tablet or powder.

<span class="mw-page-title-main">Nevirapine</span> Chemical compound

Nevirapine (NVP), sold under the brand name Viramune among others, is a medication used to treat and prevent HIV/AIDS, specifically HIV-1. It is generally recommended for use with other antiretroviral medications. It may be used to prevent mother to child spread during birth but is not recommended following other exposures. It is taken by mouth.

<span class="mw-page-title-main">Emtricitabine/tenofovir</span> Drug combination for HIV/AIDS prophylaxis and treatment

Emtricitabine/tenofovir, sold under the brand name Truvada among others, is a fixed-dose combination antiretroviral medication used to treat and prevent HIV/AIDS. It contains the antiretroviral medications emtricitabine and tenofovir disoproxil. For treatment, it must be used in combination with other antiretroviral medications. For prevention before exposure, in those who are at high risk, it is recommended along with safer sex practices. It does not cure HIV/AIDS. Emtricitabine/tenofovir is taken by mouth.

<span class="mw-page-title-main">Pre-exposure prophylaxis for HIV prevention</span> HIV prevention strategy using preventative medication for HIV-negative individuals

Pre-exposure prophylaxis for HIV prevention, commonly known as PrEP, is a form of medication used to prevent HIV infection, the cause of HIV/AIDS.

<span class="mw-page-title-main">Darunavir</span> Antiretroviral medication

Darunavir (DRV), sold under the brand name Prezista among others, is an antiretroviral medication used to treat and prevent HIV/AIDS. It is generally recommended for use with other antiretrovirals. It is often used with low doses of ritonavir or cobicistat to increase darunavir levels. It may be used for prevention after a needlestick injury or other potential exposure. It is taken by mouth once to twice a day.

<span class="mw-page-title-main">Efavirenz/emtricitabine/tenofovir</span> Combination drug for HIV

Efavirenz/emtricitabine/tenofovir, sold under the brand name Atripla among others, is a fixed-dose combination antiretroviral medication used to treat HIV/AIDS. It contains efavirenz, emtricitabine, and tenofovir disoproxil. It can be used by itself or together with other antiretroviral medications. It is taken by mouth.

Ibalizumab, sold under the brand name Trogarzo, is a non-immunosuppressive humanised monoclonal antibody that binds CD4, the primary receptor for HIV, and inhibits HIV from entering cells. It is a post-attachment inhibitor, blocking HIV from binding to the CCR5 and CXCR4 co-receptors after HIV binds to the CD4 receptor on the surface of a CD4 cell. Post-attachment inhibitors are a subclass of HIV drugs called entry inhibitors.

<span class="mw-page-title-main">Rilpivirine</span> HIV treatment

Rilpivirine, sold under the brand names Edurant and Rekambys, is a medication, developed by Tibotec, used for the treatment of HIV/AIDS. It is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with higher potency, longer half-life and reduced side-effect profile compared with older NNRTIs such as efavirenz.

<span class="mw-page-title-main">Tenofovir alafenamide</span> Chemical compound

Tenofovir alafenamide, sold under the brand name Vemlidy, is an antiviral medication used against hepatitis B and HIV. It is used for the treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disease and is given in combination with other medications for the prevention and treatment of HIV. It is taken by mouth.

Elvitegravir/cobicistat/emtricitabine/tenofovir, sold under the brand name Stribild, also known as the Quadpill, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. Elvitegravir, emtricitabine and tenofovir disoproxil directly suppress viral reproduction. Cobicistat increases the effectiveness of the combination by inhibiting the liver and gut wall enzymes that metabolize elvitegravir. It is taken by mouth. It is manufactured by Gilead Sciences.

<span class="mw-page-title-main">Cabotegravir</span> Medication for HIV/AIDS

Cabotegravir, sold under the brand name Vocabria among others, is a antiretroviral medication used for the treatment of HIV/AIDS. It is available in the form of tablets and as an intramuscular injection, as well as in an injectable combination with rilpivirine under the brand name Cabenuva.

<span class="mw-page-title-main">Fostemsavir</span> Chemical compound

Fostemsavir, sold under the brand name Rukobia, is an antiretroviral medication for adults living with HIV/AIDS who have tried multiple HIV medications and whose HIV infection cannot be successfully treated with other therapies because of resistance, intolerance or safety considerations.

<span class="mw-page-title-main">Bictegravir</span> Chemical compound

Bictegravir is a second-generation integrase inhibitor (INSTI) class that was structurally derived from an earlier compound dolutegravir by scientists at Gilead Sciences. In vitro and clinical results were presented by Gilead in the summer of 2016. In 2016, bictegravir was in a Phase 3 trial as part of a single tablet regimen in combination with tenofovir alafenamide (TAF) and emtricitabine (FTC) for the treatment of HIV-1 infection.

<span class="mw-page-title-main">Bictegravir/emtricitabine/tenofovir alafenamide</span> Fixed dose combination HIV drug

Bictegravir/emtricitabine/tenofovir alafenamide, sold under the brand name Biktarvy, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. It contains bictegravir, a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor; emtricitabine, an HIV-1 nucleoside analog reverse transcriptase inhibitor; and tenofovir alafenamide, an HIV-1 nucleoside analog reverse transcriptase inhibitor.

<span class="mw-page-title-main">Linda-Gail Bekker</span> Zimbabwean physician & academic

Linda-Gail Bekker MBChB, DTMH, DCH, FCP(SA) is a Professor of Medicine and Chief Operating Officer of the Desmond Tutu HIV Foundation. She is also Director of the Desmund Tutu HIV Centre at the University of Cape Town. She is a Past President of the International AIDS Society (2016-18).

<span class="mw-page-title-main">Cabotegravir/rilpivirine</span> Co-packaged antiretroviral medication

Cabotegravir/rilpivirine, sold under the brand name Cabenuva, is a co-packaged antiretroviral medication for the treatment of HIV/AIDS. It contains cabotegravir and rilpivirine in a package with two separate injection vials.

In the management of HIV/AIDS, HIV capsid inhibitors are antiretroviral medicines that target the capsid shell of the virus. This is in contrast to most current antiretroviral drugs used to treat HIV, which do not directly target the viral capsid. These have also been termed "Capsid-targeting Antivirals", "Capsid Effectors", and "Capsid Assembly Modulators (CAMs)". Because of this, drugs that specifically inhibit the HIV capsid are being developed in order to reduce the replication of HIV, and treat infections that have become resistant to current antiretroviral therapies.

References

  1. 1 2 "Sunlenca". Therapeutic Goods Administration. 6 April 2023. Archived from the original on 8 April 2023. Retrieved 7 April 2023.
  2. ↑ "Sunlenca lenacapavir (as sodium) 300 mg film coated tablet blister pack (392350)". Therapeutic Goods Administration. 28 March 2023. Archived from the original on 8 April 2023. Retrieved 7 April 2023.
  3. ↑ "Sunlenca lenacapavir (as sodium) 463.5 mg/1.5 mL solution for injection vial (386895)". Therapeutic Goods Administration. 28 March 2023. Archived from the original on 8 April 2023. Retrieved 7 April 2023.
  4. ↑ https://www.tga.gov.au/resources/auspar/auspar-sunlenca [ bare URL ]
  5. 1 2 3 "Sunlenca Oral Product information". Health Canada . 25 April 2012. Archived from the original on 15 January 2023. Retrieved 23 December 2022.
  6. 1 2 3 "Sunlenca Subcutaneous Product information". Health Canada . 25 April 2012. Archived from the original on 15 January 2023. Retrieved 23 December 2022.
  7. ↑ "Summary Basis of Decision - Sunlenca". Health Canada . 10 March 2023. Archived from the original on 25 April 2023. Retrieved 24 April 2023.
  8. ↑ "Details for: Sunlenca". Health Canada . 15 March 2023. Archived from the original on 3 March 2024. Retrieved 3 March 2024.
  9. 1 2 3 4 5 6 7 "Sunlenca- lenacapavir sodium tablet, film coated Sunlenca- lenacapavir sodium kit". DailyMed. 21 December 2022. Archived from the original on 21 January 2023. Retrieved 21 January 2023.
  10. 1 2 3 4 5 6 "Sunlenca EPAR". European Medicines Agency (EMA). 22 June 2022. Archived from the original on 26 August 2022. Retrieved 25 August 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  11. 1 2 3 4 5 6 7 8 9 10 11 12 "FDA Approves New HIV Drug for Adults with Limited Treatment Options" (Press release). U.S. Food and Drug Administration (FDA). 22 December 2022. Archived from the original on 15 January 2023. Retrieved 23 December 2022.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  12. ↑ "Gilead Announces First Global Regulatory Approval of Sunlenca (Lenacapavir), the Only Twice-Yearly HIV Treatment Option". Gilead Sciences, Inc. (Press release). 22 August 2022. Archived from the original on 15 January 2023. Retrieved 23 December 2022.
  13. ↑ "Sunlenca (lenacapavir) Receives FDA Approval as a First-in-Class, Twice-Yearly Treatment Option for People Living With Multi-Drug Resistant HIV". Gilead Sciences, Inc. (Press release). 22 December 2022. Archived from the original on 23 December 2022. Retrieved 23 December 2022.
  14. ↑ Paik J (September 2022). "Lenacapavir: First Approval". Drugs. 82 (14): 1499–1504. doi:10.1007/s40265-022-01786-0. PMC   10267266 . PMID   36272024.
  15. 1 2 "Advancing Health Through Innovation: New Drug Therapy Approvals 2022". U.S. Food and Drug Administration . 10 January 2023. Archived from the original on 21 January 2023. Retrieved 22 January 2023.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  16. ↑ Bekker LG, Das M, Abdool Karim Q, Ahmed K, Batting J, Brumskine W, et al. (July 2024). "Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women". The New England Journal of Medicine. doi:10.1056/NEJMoa2407001. PMID   39046157.
  17. ↑ "Prevention With a Purpose". purposestudies.com.
  18. ↑ New Drug Therapy Approvals 2022 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2024. Archived from the original on 14 January 2024. Retrieved 14 January 2024.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  19. ↑ Link JO, Rhee MS, Tse WC, Zheng J, Somoza JR, Rowe W, et al. (August 2020). "Clinical targeting of HIV capsid protein with a long-acting small molecule". Nature. 584 (7822): 614–618. Bibcode:2020Natur.584..614L. doi:10.1038/s41586-020-2443-1. PMC   8188729 . PMID   32612233. S2CID   220293679.
  20. 1 2 "Sunlenca: Pending EC decision". European Medicines Agency. 23 June 2022. Archived from the original on 26 June 2022. Retrieved 26 June 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  21. ↑ "Sunlenca Product information". Union Register of medicinal products. Archived from the original on 3 March 2023. Retrieved 3 March 2023.
  22. ↑ "AIDS 2024, the 25th International AIDS Conference". International AIDS Society (IAS). Retrieved 23 July 2024.
  23. ↑ Lay K (23 July 2024). "HIV 'vaccine' could be made for just $40 a year for every patient". The Guardian.
  24. 1 2 Boerner H (11 March 2021). "Lenacapavir Effective in Multidrug Resistant HIV". Medscape. Archived from the original on 16 March 2021. Retrieved 15 March 2021.
  25. ↑ Highleyman L (15 March 2021). "Lenacapavir Shows Promise for Long-Acting HIV Treatment and Prevention". POZ. Archived from the original on 19 July 2021.
  26. ↑ Gupta S (January 2023). "Lenacapavir administered every 26 weeks or daily in combination with oral daily antiretroviral therapy for initial treatment of HIV: a randomised, open-label, active-controlled, phase 2 trial". The Lancet HIV. 10 (1): 15–23. doi:10.1016/S2352-3018(22)00291-0. PMID   36566079 . Retrieved 10 March 2024.
  27. ↑ Highleyman L (28 February 2023). "Lenacapavir plus broadly neutralising antibodies may offer twice-yearly treatment option". Aidsmap. Retrieved 10 March 2024.
  28. ↑ Highleyman L (6 March 2024). "Islatravir plus lenacapavir could be the first once-weekly oral HIV treatment". Aidsmap. Retrieved 10 March 2024.
  29. ↑ Bekker LG, Das M, Abdool Karim Q, Ahmed K, Batting J, Brumskine W, et al. (July 2024). "Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women". The New England Journal of Medicine. doi:10.1056/NEJMoa2407001. PMID   39046157.
  30. ↑ "Lenacapavir Shows 100% Efficacy and Zero Infections in HIV Prevention". www.precisionvaccinations.com. Retrieved 25 July 2024.
  31. ↑ "Full Efficacy and Safety Results for Gilead Investigational Twice-Yearly Lenacapavir for HIV Prevention Presented at AIDS 2024". www.gilead.com. Retrieved 25 July 2024.
  32. ↑ Bekker LG (3 July 2024). "HIV breakthrough: drug trial shows injection twice a year is 100% effective against infection". The Conversation. Retrieved 25 July 2024.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.