Lenacapavir Explained

Tradename:Sunlenca
Dailymedid:Lenacapavir
Pregnancy Au:B1
Pregnancy Au Comment:[1]
Routes Of Administration:By mouth, subcutaneous
Class:Capsid inhibitors
Atc Prefix:J05
Atc Suffix:AX31
Legal Au:S4
Legal Au Comment:[2] [3] [4]
Legal Ca:Rx-only
Legal Ca Comment:[5] [6] [7] [8]
Legal Us:Rx-only
Legal Us Comment:[9]
Legal Eu:Rx-only
Legal Eu Comment:[10]
Cas Number:2189684-44-2
Drugbank:DB15673
Chemspiderid:81367881
Unii:A9A0O6FB4H
Kegg:D12161
Kegg2:D12162
Chembl:4594438
Pdb Ligand:QNG
Synonyms:GS-CA1, GS-6207
Iupac Name: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
C:39
H:32
Cl:1
F:10
N:7
O:5
S:2
Smiles: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
Stdinchi: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
Stdinchikey:BRYXUCLEHAUSDY-WEWMWRJBSA-N

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

The most common side effects include reactions at the injection site and nausea.

Lenacapavir was approved for medical treatment in the European Union in August 2022,[11] in Canada in November 2022, and in the United States in December 2022.[12] [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.

Medical uses

Lenacapavir, in combination with other antiretrovirals, is indicated for the treatment of HIV/AIDS. 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.

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, virus assembly and release, production of capsid protein subunits, and capsid core formation. The US Food and Drug Administration considers it to be a first-in-class medication.[15] [16]

History

Lenacapavir was developed by Gilead Sciences.[17]

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. These participants had to have high levels of virus in their blood despite being on antiretroviral drugs. Participants were enrolled into one of two study groups. One group was randomized to receive either lenacapavir or placebo in a double-blind fashion, and the other group received open-label lenacapavir. 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.

The U.S. Food and Drug Administration granted the application for lenacapavir priority review, fast track, and breakthrough therapy designations.

Society and culture

Legal status

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. The applicant for this medicinal product is Gilead Sciences Ireland UC.[18]

Lenacapavir was approved for medical use in the European Union in August 2022,[19] in Canada in November 2022, and in the United States in December 2022.

Economics

the drug, produced by Gilead, costs for the first year. A study presented in July 2024[20] 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.[21]

Research

As of 2021, it is in phase II/III clinical trials.[22] 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.[22] [23]

Studies have been conducted for the use of lenacapavir in treatment-naive individuals.[24] For virally suppressed individuals switching treatment, early studies have tested lenacapavir injections in combination with infusions of the broadly neutralizing antibodies teropavimab and zinlirvimab[25] as well as lenacapavir with islatravir.[26]

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.[27] [28] [29] [30]

External links

Notes and References

  1. Web site: Sunlenca . Therapeutic Goods Administration . 6 April 2023 . 7 April 2023 . 8 April 2023 . https://web.archive.org/web/20230408034856/https://www.tga.gov.au/resources/auspmd/sunlenca . live .
  2. Web site: Sunlenca lenacapavir (as sodium) 300 mg film coated tablet blister pack (392350) . Therapeutic Goods Administration . 28 March 2023 . 7 April 2023 . 8 April 2023 . https://web.archive.org/web/20230408034855/https://www.tga.gov.au/resources/artg/392350 . live .
  3. Web site: Sunlenca lenacapavir (as sodium) 463.5 mg/1.5 mL solution for injection vial (386895) . Therapeutic Goods Administration . 28 March 2023 . 7 April 2023 . 8 April 2023 . https://web.archive.org/web/20230408034858/https://www.tga.gov.au/resources/artg/386895 . live .
  4. https://www.tga.gov.au/resources/auspar/auspar-sunlenca
  5. Web site: Sunlenca Oral Product information . . 25 April 2012 . 23 December 2022 . 15 January 2023 . https://web.archive.org/web/20230115194229/https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=102149 . live .
  6. Web site: Sunlenca Subcutaneous Product information . . 25 April 2012 . 23 December 2022 . 15 January 2023 . https://web.archive.org/web/20230115164647/https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=102150 . live .
  7. Web site: Summary Basis of Decision - Sunlenca . . 10 March 2023 . 24 April 2023 . 25 April 2023 . https://web.archive.org/web/20230425001504/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00627&lang=en . live .
  8. Web site: Details for: Sunlenca . . 15 March 2023 . 3 March 2024 . 3 March 2024 . https://web.archive.org/web/20240303062559/https://dhpp.hpfb-dgpsa.ca/dhpp/resource/102149 . live .
  9. Web site: Sunlenca- lenacapavir sodium tablet, film coated Sunlenca- lenacapavir sodium kit . DailyMed . 21 December 2022 . 21 January 2023 . 21 January 2023 . https://web.archive.org/web/20230121044750/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e5652804-29c4-40d7-aeb2-0142ed2a7b5b . live .
  10. Web site: Sunlenca EPAR . European Medicines Agency (EMA) . 22 June 2022 . 25 August 2022 . 26 August 2022 . https://web.archive.org/web/20220826024847/https://www.ema.europa.eu/en/medicines/human/EPAR/sunlenca . live . Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  11. Gilead Announces First Global Regulatory Approval of Sunlenca (Lenacapavir), the Only Twice-Yearly HIV Treatment Option . Gilead Sciences, Inc. . 22 August 2022 . 23 December 2022 . 15 January 2023 . https://web.archive.org/web/20230115164646/https://www.gilead.com/news-and-press/press-room/press-releases/2022/8/gilead-announces-first-global-regulatory-approval-of-sunlenca-lenacapavir-the-only-twiceyearly-hiv-treatment-option . live .
  12. FDA Approves New HIV Drug for Adults with Limited Treatment Options . U.S. Food and Drug Administration (FDA) . 22 December 2022 . 23 December 2022 . 15 January 2023 . https://web.archive.org/web/20230115164646/https://www.fda.gov/news-events/press-announcements/fda-approves-new-hiv-drug-adults-limited-treatment-options . live .
  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. . 22 December 2022 . 23 December 2022 . 23 December 2022 . https://web.archive.org/web/20221223070110/https://www.gilead.com/news-and-press/press-room/press-releases/2022/12/sunlenca-lenacapavir-receives-fda-approval-as-a-firstinclass-twiceyearly-treatment-option-for-people-living-with-multidrug-resistant-hiv . live .
  14. Paik J . Lenacapavir: First Approval . Drugs . 82 . 14 . 1499–1504 . September 2022 . 36272024 . 10267266 . 10.1007/s40265-022-01786-0 .
  15. Web site: Advancing Health Through Innovation: New Drug Therapy Approvals 2022 . . 10 January 2023 . 22 January 2023 . 21 January 2023 . https://web.archive.org/web/20230121035714/https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2022 . live .
  16. New Drug Therapy Approvals 2022 . U.S. Food and Drug Administration (FDA) . January 2024 . PDF . 14 January 2024 . https://web.archive.org/web/20240114065648/https://www.fda.gov/media/164429/download . 14 January 2024 . live .
  17. Link JO, Rhee MS, Tse WC, Zheng J, Somoza JR, Rowe W, Begley R, Chiu A, Mulato A, Hansen D, Singer E, Tsai LK, Bam RA, Chou CH, Canales E, Brizgys G, Zhang JR, Li J, Graupe M, Morganelli P, Liu Q, Wu Q, Halcomb RL, Saito RD, Schroeder SD, Lazerwith SE, Bondy S, Jin D, Hung M, Novikov N, Liu X, Villaseñor AG, Cannizzaro CE, Hu EY, Anderson RL, Appleby TC, Lu B, Mwangi J, Liclican A, Niedziela-Majka A, Papalia GA, Wong MH, Leavitt SA, Xu Y, Koditek D, Stepan GJ, Yu H, Pagratis N, Clancy S, Ahmadyar S, Cai TZ, Sellers S, Wolckenhauer SA, Ling J, Callebaut C, Margot N, Ram RR, Liu YP, Hyland R, Sinclair GI, Ruane PJ, Crofoot GE, McDonald CK, Brainard DM, Lad L, Swaminathan S, Sundquist WI, Sakowicz R, Chester AE, Lee WE, Daar ES, Yant SR, Cihlar T . Clinical targeting of HIV capsid protein with a long-acting small molecule . Nature . 584 . 7822 . 614–618 . August 2020 . 32612233 . 10.1038/s41586-020-2443-1 . 220293679 . 2020Natur.584..614L . 8188729 .
  18. Web site: Sunlenca: Pending EC decision . European Medicines Agency . 23 June 2022 . 26 June 2022 . 26 June 2022 . https://web.archive.org/web/20220626031517/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/sunlenca . live . Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  19. Web site: Sunlenca Product information . Union Register of medicinal products . 3 March 2023 . 3 March 2023 . https://web.archive.org/web/20230303202158/https://ec.europa.eu/health/documents/community-register/html/h1671.htm . live .
  20. Web site: AIDS 2024, the 25th International AIDS Conference. International AIDS Society (IAS) . 23 July 2024.
  21. News: Lay K . HIV 'vaccine' could be made for just $40 a year for every patient . The Guardian . 23 July 2024 .
  22. Web site: Boerner H . 11 March 2021 . Lenacapavir Effective in Multidrug Resistant HIV . Medscape . 15 March 2021 . 16 March 2021 . https://web.archive.org/web/20210316002459/https://www.medscape.com/viewarticle/947319 . live .
  23. Web site: Highleyman L. Lenacapavir Shows Promise for Long-Acting HIV Treatment and Prevention. 15 March 2021. POZ. 19 July 2021. https://web.archive.org/web/20210719001953/https://www.poz.com/article/lenacapavir-shows-promise-longacting-hiv-treatment-prevention. live.
  24. Gupta S . 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 . January 2023 . 10 . 1 . 15–23 . 10.1016/S2352-3018(22)00291-0 . 36566079 . 10 March 2024.
  25. Web site: Highleyman L . Lenacapavir plus broadly neutralising antibodies may offer twice-yearly treatment option . Aidsmap . 10 March 2024 . 28 February 2023.
  26. Web site: Highleyman L . Islatravir plus lenacapavir could be the first once-weekly oral HIV treatment . Aidsmap . 10 March 2024 . 6 March 2024.
  27. Bekker LG, Das M, Abdool Karim Q, Ahmed K, Batting J, Brumskine W, Gill K, Harkoo I, Jaggernath M, Kigozi G, Kiwanuka N, Kotze P, Lebina L, Louw CE, Malahleha M, Manentsa M, Mansoor LE, Moodley D, Naicker V, Naidoo L, Naidoo M, Nair G, Ndlovu N, Palanee-Phillips T, Panchia R, Pillay S, Potloane D, Selepe P, Singh N, Singh Y, Spooner E, Ward AM, Zwane Z, Ebrahimi R, Zhao Y, Kintu A, Deaton C, Carter CC, Baeten JM, Matovu Kiweewa F . Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women . The New England Journal of Medicine . July 2024 . 39046157 . 10.1056/NEJMoa2407001 .
  28. Web site: Lenacapavir Shows 100% Efficacy and Zero Infections in HIV Prevention . 25 July 2024 . www.precisionvaccinations.com .
  29. Web site: Full Efficacy and Safety Results for Gilead Investigational Twice-Yearly Lenacapavir for HIV Prevention Presented at AIDS 2024 . 25 July 2024 . www.gilead.com .
  30. Web site: Bekker LG . 3 July 2024 . HIV breakthrough: drug trial shows injection twice a year is 100% effective against infection . 25 July 2024 . The Conversation .

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