Drug information

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Other Names
LEN, GS-6207, GS-CA2
Drug Class
Capsid Inhibitors
Molecular Formula

C39 H32 Cl F10 N7 O5 S2

Registry Number
2189684-44-2 (CAS)
Chemical Name

1H-Cyclopropa[3,4]cyclopenta[1,2-c]pyrazole, N-[(1S)-1-[3-[4-chloro-3-[(methylsulfonyl)amino]-1-(2,2,2-trifluoroethyl)- 1H-indazol-7-yl]-6-[3-methyl-3-(methylsulfonyl)-1-butyn-1-yl]-2-pyridinyl]- 2-(3,5-difluorophenyl)ethyl]-5,5-difluoro-3b,4,4a,5-tetrahydro-3- (trifluoromethyl)-, (3bS,4aR)-

Organization
Gilead Sciences, Inc.
Phase of Development

Lencacapvir is in Phase 2/3 development for HIV treatment and Phase 3 development for HIV prevention.


An application for marketing approval of lenacapavir for the treatment of HIV infection in heavily treatment-experienced people with multidrug-resistant HIV was submitted to the U.S. Food and Drug Administration (FDA) in June 2021. FDA issued a complete response letter in March 2022, indicating that the application was not ready for approval because of issues relating to the compatibility of lenacapavir solution and container vials.

(Compound details obtained from NIAID Therapeutics Database,1 American Medical Association website,2ClinicalTrials.gov,3-5 and Gilead press release6,7)

What is lenacapavir?What is lenacapavir?

What is lenacapavir?

Lenacapavir is an investigational drug that is being studied to treat and prevent HIV infection.3-5,8

Lenacapavir belongs to a group of HIV drugs called capsid inhibitors.1 Capsid inhibitors interfere with HIV capsid, a protein shell that protects HIV’s genetic material and enzymes needed for replication. Capsid inhibitors can disrupt HIV capsid during multiple stages of the viral life cycle. This prevents HIV from multiplying and can reduce the amount of HIV in the body.9,10

Lenacapavir may work against HIV strains that are resistant to other HIV drugs.11

To learn about how investigational drugs are tested during clinical trials, read the HIVinfo What is an Investigational HIV Drug? and HIV and AIDS Clinical Trials fact sheets.

Select clinical trials of lenacapavirSelect clinical trials of lenacapavir

Select clinical trials of lenacapavir

Lenacapavir for HIV Treatment

Study Names: CALIBRATE; GS-US-200-4334; NCT04143594
Phase: 2
Status: This study is ongoing, but not recruiting participants.
Locations: United States, Dominican Republic, and Puerto Rico
Purpose: The purpose of this study is to evaluate the efficacy of subcutaneous and oral lenacapavir when given in combination with other antiretroviral agents in adults with HIV who have never taken HIV medicines.8
Selected Study Results: Week 54 results presented at CROI 2022 showed that subcutaneous lenacapavir given every 6 months, initially in combination with emtricitabine/tenofovir alafenamide (brand name: Descovy) and later in combination with tenofovir alafenamide or bictegravir, achieved high rates of viral viral suppression, comparable to oral daily bictegravir/emtricitabine/tenofovir alafenamide (brand name: Biktarvy). Similar efficacy results were seen with oral lenacapavir in combination with Descovy.12


Study Names: CAPELLA; GS-US-200-4625; NCT04150068
Phase: 2/3
Status: This study is ongoing, but not recruiting participants.
Locations: Multiple countries, including United States
Purpose: The primary purpose of this study is to evaluate the efficacy of oral lenacapavir given as an add-on to a failing antiretroviral therapy (ART) regimen over 14 days in participants with mutidrug-resistant HIV. Afterwards, the efficacy of subcutaneous lenacapavir given in combination with optimized background therapy will be assessed.3
Selected Study Results: Results presented at CROI 2021 showed that a significantly higher proportion of participants receiving oral lenacapavir than participants receiving placebo achieved a substantial decline in viral load levels during the 14-day functional monotherapy period.13
Additional Published Material:


Study Names: GS-US-563-6041; NCT05052996
Phase: 2
Status: See note below. Please refer to the ClinicalTrials.gov record and/or the drug developer’s website for updates on this study’s status.
Location: United States
Purpose: The purpose of this study is to evaluate the efficacy of the investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI) islatravir in combination with oral lenacapavir in participants with viral suppression on Biktarvy.14
Note: The developers of islatravir and lenacapavir have decided to stop all dosing of participants in the GS-US-563-6041 trial. Participants will discontinue study treatment and restart their prior antiretroviral regimen. Please see this December 13, 2021 press release for more details.15


Additional early-phase studies evaluating lenacapavir for HIV treatment have been conducted, including:

  • GS-US-200-4072 (NCT03739866) A Phase 1b trial that evaluated the safety, pharmacokinetics and antiviral activity of subcutaneous lenacapavir in adults with HIV. This study has been completed.16
  • GS-US-536-5816 (NCT04811040): A Phase 1b trial investigating the safety and efficacy of the investigational broadly neutralizing antibodies (bNAbs) GS-5423 and GS-2872 in combination with lenacapavir in adults with HIV who have viral suppression. This study is ongoing, but not recruiting participants.17


Lenacapavir for HIV prevention

Study Names: PURPOSE 1; GS-US-412-5624; NCT04994509
Phase: 3
Status: This study is ongoing, but not recruiting participants.
Location: South Africa
Purpose: The purpose of this two-part study is to 1) estimate the background HIV incidence rate, and 2) evaluate the efficacy of twice yearly subcutaneous lenacapavir and daily oral Descovy for pre-exposure prophylaxis (PrEP) in adolescent girls and young women who are at risk of acquiring HIV infection.4


Study Names: PURPOSE 2; GS-US-528-9023; NCT04925752
Phase: 3
Status: This study is ongoing, but not recruiting participants.
Locations: United States, Puerto Rico, and South Africa
Purpose: The purpose of this two-part study is to 1) estimate the background HIV incidence rate, and 2) evaluate the efficacy of twice yearly subcutaneous lenacapavir for PrEP in cisgender men, transgender women, transgender men, and gender nonbinary people who have sex with partners assigned male at brith and are at risk of acquiring HIV infection.5

For more details on the studies listed above, see the Health Professional version of this drug summary.

What side effects might lencapavir cause?What side effects might lencapavir cause?

What side effects might lencapavir cause?

One goal of HIV research is to identify new drugs that have fewer side effects. The following side effects were observed in some of the studies of lenacapavir listed above.

CALIBRATE (NCT04143594):

In the CALIBRATE study, Week 54 results showed that the most common side effects (excluding injection site reactions) in participants who received oral or subcutaneous lenacapavir were headache, nausea, and Covid-19 infection. No participant experienced a drug-related serious or life-threatening side effect.8,12

Most injection site reactions related to subcutaneous lenacapavir injections were mild or moderate in severity and included temporary skin redness (erythema), swelling, and pain. Lumps (nodules) and hardening of the skin/tissue around the injection site (induration) also occurred in some participants and lasted for several months. One participant had a severe nodule occur after receiving their second dose of subcutaneous lenacapavir. Three participants stopped lenacapavir treatment because of injection site reactions – two were due to mild induration and one was due to mild erythema and swelling.12,18

CAPELLA (NCT04150068):

In the CAPELLA study, Week 52 results showed that among participants who received oral and subcutaneous lenacapavir, there were no drug-related serious side effects. Excluding injection site reactions, common side effects that occurred during the study included nausea, diarrhea, and Covid-19.3,19

Injection site reactions related to subcutaneous lenacapavir injections occurred in 63% of participants and included pain, swelling, erythema, nodule, and induration. Most injection site reactions were mild or moderate in severity and went away within days. Nodules and induration, however, lasted several months. Two participants had temporary injection site reactions that were severe – swelling and erythema in one participant and pain in the other participant. One participant stopped treatment at Week 52 because of a mild nodule.19,20

Because lenacapavir is still being studied, information on possible side effects of the drug is not complete. As testing of lenacapavir continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying lenacapavir?Where can I get more information about clinical trials studying lenacapavir?

Where can I get more information about clinical trials studying lenacapavir?

More information about lenacapavir-related research studies is available from ClinicalTrials.gov.

Some clinical trials may be looking for volunteer participants. Your health care provider can help you decide whether participating in a clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.

References

  1. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed May 18, 2022
  2. American Medical Association (AMA) website. Statement on a nonproprietary name adopted by the USAN council: lenacapavir. https://searchusan.ama-assn.org/usan/documentDownload?uri=/unstructured/binary/usan/lenacapavir-.pdf. Accessed May 18, 2022
  3. Gilead Sciences. A Phase 2/3 study to evaluate the safety and efficacy of long acting capsid inhibitor GS-6207 in combination with an optimized background regimen in heavily treatment experienced people living with HIV-1 infection with multidrug resistance. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 28, 2019. NLM Identifier: NCT04150068. https://clinicaltrials.gov/ct2/show/NCT04150068. Accessed May 18, 2022
  4. Gilead Sciences. A Phase 3, double-blinded, multicenter, randomized study to evaluate safety and efficacy of twice yearly long-acting subcutaneous lenacapavir, and daily oral emtricitabine/tenofovir alafenamide for pre-exposure prophylaxis in adolescent girls and young women at risk of HIV infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 2, 2021. NLM Identifier: NCT04994509. https://clinicaltrials.gov/ct2/show/NCT04994509. Accessed May 18, 2022
  5. Gilead Sciences. A Phase 3, double-blind, multicenter, randomized study to evaluate the efficacy and safety of subcutaneous twice yearly long-acting lenacapavir for HIV pre-exposure prophylaxis in cisgender men, transgender women, transgender men, and gender non-binary people ≥ 16 years of age who have sex with partners assigned male at birth and are at risk for HIV infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 28, 2021. NLM Identifier: NCT04925752. https://www.clinicaltrials.gov/ct2/show/NCT04925752. Accessed May 18, 2022
  6. Gilead Sciences: Press Release, dated June 28, 2021. Gilead submits new drug application to U.S. Food and Drug Administration for lenacapavir, an investigational, long-acting capsid inhibitor for the treatment of HIV-1 in people with limited therapy options. https://www.gilead.com/news-and-press/press-room/press-releases/2021/6/gilead-submits-new-drug-application-to-us-food-and-drug-administration-for-lenacapavir-an-investigational-longacting-capsid-inhibitor-for-the-tre. Accessed May 18, 2022
  7. Gilead Sciences: Press Release, dated March 1, 2022. Gilead receives complete response letter from U.S. FDA for investigational lenacapavir due to vial compatibility issues. https://www.gilead.com/news-and-press/press-room/press-releases/2022/3/gilead-receives-complete-response-letter-from-us-fda-for-investigational-lenacapavir-due-to-vial-compatibility-issues. Accessed May 18, 2022
  8. Gilead Sciences. A Phase 2 randomized, open label, active controlled study evaluating the safety and efficacy of long-acting capsid inhibitor GS-6207 in combination with other antiretroviral agents in people living with HIV. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 28, 2019. NLM Identifier: NCT04143594. https://clinicaltrials.gov/ct2/show/NCT04143594. Accessed May 18, 2022
  9. Collins S and Clayden P. HIV pipeline 2020: new drugs in development. HIV Treatment Bulletin. 2020 Mar; 21(1) Suppl: 1-13. https://i-base.info/htb/wp-content/uploads/2020/03/i-Base-HIV-pipeline-March-2020.pdf. Accessed May 18, 2022
  10. Carnes SK, Sheehan JH, Aiken C. Inhibitors of the HIV-1 Capsid, A Target of Opportunity. Curr Opin HIV AIDS. 2018;13(4):359-365. doi:10.1097/COH.0000000000000472
  11. Rhee, M. Lenacapavir (GS-6207): a first-in-class long acting HIV capsid inhibitor. HIV DART; December 10, 2020; Virtual Meeting. National AIDS Treatment Advocacy Project (NATAP): HIV Articles; 2020. https://www.natap.org/2020/HIV/121520_02.htm. Accessed May 18, 2022
  12. Gupta SK, Sims J, Brinson C, et al. Lenacapavir as part of a combination regimen in treatment naïve PWH: Week 54 results. Webcast presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 12-16, 2022; Virtual. http://www.croiwebcasts.org/console/player/50587?mediaType=slideVideo&. Accessed May 18, 2022
  13. Segal-Maurer S, Castagna A, Berhe M, et al. Potent antiviral activity of lenacapavir in Phase 2/3 in heavily ART-experienced PWH. Webcast presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 6-11, 2021; Virtual. http://www.croiwebcasts.org/console/player/48167?mediaType=slideVideo&. Accessed May 18, 2022
  14. Gilead Sciences. A Phase 2 randomized, open-label, active-controlled study evaluating the safety and efficacy of an oral weekly regimen of islatravir in combination with lenacapavir in virologically suppressed people with HIV. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 13, 2021. NLM Identifier: NCT05052996. https://clinicaltrials.gov/ct2/show/NCT05052996
  15. Merck: Press release, dated December 13, 2021. Merck announces clinical holds on studies evaluating islatravir for the treatment and prevention of HIV-1 infection. https://www.merck.com/news/merck-announces-clinical-holds-on-studies-evaluating-islatravir-for-the-treatment-and-prevention-of-hiv-1-infection/. Accessed May 18, 2022
  16. Gilead Sciences. A Phase 1b randomized, double-blinded, placebo controlled, multi-cohort study of the safety, pharmacokinetics, and antiviral activity of GS-6207 administered subcutaneously in HIV-1 infected subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 2, 2018. NLM Identifier: NCT03739866. https://clinicaltrials.gov/ct2/show/NCT03739866. Accessed May 18, 2022
  17. Gilead Sciences. A Phase 1b randomized, blinded, proof-of-concept study to evaluate the safety and efficacy of broadly neutralizing antibodies (bNAbs) GS-5423 and GS-2872 in combination with capsid inhibitor lenacapavir (GS-6207) in virologically suppressed adults with HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 19, 2021. NLM Identifier: NCT04811040. https://clinicaltrials.gov/ct2/show/NCT04811040. Accessed May 18, 2022
  18. Gupta SK, Sims J, Brinson C, et al. Lenacapavir as part of a combination regimen in treatment naïve PWH: Week 54 results. Abstract presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 12-16, 2022; Virtual. https://www.croiconference.org/abstract/lenacapavir-as-part-of-a-combination-regimen-in-treatment-naive-pwh-week-54-results/. Accessed May 18, 2022
  19. Ogbuagu O, Segal-Maurer S, Brinson C, et al. Long-acting lenacapavir in people with multidrug resistant HIV-1: Week 52 results. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 12-16, 2022; Virtual. https://2jg4quetidw2blbbq2ixwziw-wpengine.netdna-ssl.com/wp-content/uploads/sites/2/posters/2022/CROI2022_Poster_491.pdf. Accessed May 18, 2022
  20. Ogbuagu O, Segal-Maurer S, Brinson C, et al. Long-acting lenacapavir in people with multidrug resistant HIV-1: Week 52 results. Abstract presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 12-16, 2022; Virtual. https://www.croiconference.org/abstract/long-acting-lenacapavir-in-people-with-multidrug-resistant-hiv-1-week-52-results/. Accessed May 18, 2022

Last Reviewed: May 18, 2022