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

C39 H31 Cl F10 N7 Na O5 S2

Registry Number
2283356-12-5 (CAS)
Chemical Name

sodium;[4-chloro-7-[2-[(1S)-2-(3,5-difluorophenyl)-1-[[2-[(2S,4R)-5,5-difluoro-9-(trifluoromethyl)-7,8-diazatricyclo[4.3.0.02,4]nona-1(6),8-dien-7-yl]acetyl]amino]ethyl]-6-(3-methyl-3-methylsulfonylbut-1-ynyl)pyridin-3-yl]-1-(2,2,2-trifluoroethyl)indazol-3-yl]-methylsulfonylazanide

Organization:
Gilead Sciences, Inc.
Phase of Development

Lenacapavir is in Phase 3 development for HIV prevention.

FDA-Approved Products for HIV Treatment: Lenacapavir (brand name: Sunlenca), in combination with other antiretrovirals, is approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV in heavily treatment-experienced adults with multidrug-resistant HIV.

(Compound details obtained from PubChem,1 ClinicalTrials.gov,2,3 and Gilead press release4)

What is lenacapavir (HIV prevention)?What is lenacapavir (HIV prevention)?

What is lenacapavir (HIV prevention)?

Lenacapavir is a drug that has been approved by the U.S. Food and Drug Administration (FDA) under the brand name Sunlenca for the treatment of HIV.4 Lenacapavir is also being studied as an investigational drug to prevent HIV infection.2,3

Lenacapavir belongs to a group of HIV drugs called capsid inhibitors.4 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.5-8 

Lenacapavir may work against HIV strains that are resistant to other HIV drugs.6

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.

Which clinical trials are studying lenacapavir (HIV prevention)?Which clinical trials are studying lenacapavir (HIV prevention)?

Which clinical trials are studying lenacapavir (HIV prevention)?

Study Names: PURPOSE 1; GS-US-412-5624; NCT04994509

Phase: 3
Status: This study is ongoing, but not recruiting participants.
Locations: South Africa and Uganda
Purpose: The purpose of this study is to evaluate the safety and efficacy of twice-yearly subcutaneous lenacapavir and daily oral emtricitabine/tenofovir alafenamide (brand name: Descovy) for pre-exposure prophylaxis (PrEP) in adolescent girls and young women who are at risk of acquiring HIV infection.2
Selected Study Results: Results presented at AIDS 2024  and published in the N Engl J Med (2024) showed that none of the women who received twice-yearly lenacapavir injections acquired HIV. HIV incidence with lenacapavir was significantly lower compared to background HIV incidence and HIV incidence with emtricitabine/tenofovir DF (Truvada). HIV incidence with Descovy was not significantly different than background HIV incidence. Notably, researchers found that adherence to lenacapavir injections was high but adherence to oral Truvada and Descovy was low.9,10

Study Names: PURPOSE 2; GS-US-528-9023; NCT04925752

Phase: 3
Status: This study is ongoing, but not recruiting participants.
Locations: United States, Brazil, Puerto Rico, and South Africa
Purpose: The purpose of this study is to evaluate the safety and efficacy of twice-yearly subcutaneous lenacapavir and daily oral emtricitabine/tenofovir DF (brand name: Truvada) for PrEP in cisgender men, transgender women, transgender men, and gender nonbinary people who have sex with partners assigned male at birth and are at risk of acquiring HIV infection.3
Selected Study Results: Results presented at HIVR4P 2024 showed that among the participants who received twice-yearly lenacapavir injections, 99.9% of participants did not acquire HIV and only two participants acquired HIV. Lenacapavir reduced HIV incidence by 96% compared with background HIV incidence. Also, when compared to Truvada, lenacapavir was shown to be more effective in preventing HIV.11

Study Names: PURPOSE 3; HPTN-102; GS-US-528-6020; NCT06101329

Phase: 2
Status: This study is currently recruiting participants.
Locations: United States
Purpose: The purpose of this study is to evaluate the pharmacokinetics of twice-yearly subcutaneous lenacapavir and to assess the safety and acceptability of twice-yearly subcutaneous lenacapavir and daily oral Truvada for PrEP in cisgender women in the United States.12

Study Names: PURPOSE 4; HPTN-103; GS-US-528-6363; NCT06101342

Phase: 2
Status: This study is currently recruiting participants.
Locations: United States
Purpose: The purpose of this study is to evaluate the pharmacokinetics of twice-yearly subcutaneous lenacapavir and to assess the safety of twice-yearly subcutaneous lenacapavir and daily oral Truvada for PrEP in people who inject drugs in the United States.13

Study Names: PURPOSE 5; GS-US-528-6727; NCT06513312  

Phase: 2 
Status: This study is currently recruiting participants.
Location: Not available.
Study Purpose: The purpose of this study is to evaluate the persistence, safety, acceptability, and pharmacokinetics of twice-yearly subcutaneous lenacapavir for PrEP in people who would benefit from PrEP.14

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

What side effects might lenacapavir (HIV prevention) cause?What side effects might lenacapavir (HIV prevention) cause?

What side effects might lenacapavir (HIV prevention) 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.

PURPOSE 1 (NCT04994509) 

In the PURPOSE 1 trial, no safety concerns were seen. Side effects associated with lenacapavir were comparable to what has been observed in previous studies. Injection-site reactions  occurred more frequently in participants receiving lenacapavir injections than in participants receiving placebo injections. The incidence of injection-site reactions associated with lenacapavir decreased with subsequent injections. Four participants in the lenacapavir group discontinued treatment because of injection-site reactions.9,10

PURPOSE 2 (NCT04925752)

In the PURPOSE 2 trial, the safety profile of lenacapavir was consistent with what has been seen in previous studies. The most common injection-site reactions reported were hardened skin or lumps (nodules), redness, and pain. The majority of these reactions were mild or moderate in severity. Nodules occurred more frequently with lenacapavir than with placebo. The incidence of injection-site reactions, including nodules, decreased over time. Twenty-six participants receiving lenacapavir discontinued treatment because of injection-site reactions.11

Additional information on side effects known to be associated with lenacapavir treatment can be found in the FDA-approved Full Prescribing Information for Sunlenca.6

Where can I get more information about clinical trials studying lenacapavir (HIV prevention)?Where can I get more information about clinical trials studying lenacapavir (HIV prevention)?

Where can I get more information about clinical trials studying lenacapavir (HIV prevention)?

More information about lenacapavir-related research studies is available from ClinicalTrials.gov. (The ClinicalTrials.gov search can be modified so that you can get results that better match your interests.)

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 Center for Biotechnology Information. PubChem compound summary for CID 153435888, lenacapavir sodium. Accessed November 19, 2024
  2. 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. Accessed November 19, 2024
  3. 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 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. Accessed November 19, 2024
  4. Gilead Sciences: Press release, dated December 22, 2022. Sunlenca® (lenacapavir) receives FDA approval as a first-in-class, twice-yearly treatment option for people living with multi-drug resistant HIV. Accessed November 19, 2024
  5. 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. Accessed November 19, 2024
  6. Gilead Sciences, Inc. Sunlenca: full prescribing information, July 30, 2024. DailyMed. Accessed November 19, 2024
  7. Link JO, Rhee MS, Tse WC, et al. Clinical targeting of HIV capsid protein with a long-acting small molecule. Nature. 2020;584(7822):614-618. doi:10.1038/s41586-020-2443-1. Accessed November 19, 2024
  8. Bester SM, Wei G, Zhao H, et al. Structural and mechanistic bases for a potent HIV-1 capsid inhibitor. Science. 2020;370(6514):360-364. doi:10.1126/science.abb4808. Accessed November 19, 2024
  9. Bekker L-G. Twice-yearly lenacapavir or daily emtricitabine/tenofovir alafenamide for HIV prevention in cisgender women: interim analysis results from the PURPOSE 1 study. Presented at: International AIDS Conference; July 22-26, 2024; Munich, Germany and Virtual. Accessed November 19, 2024
  10. Bekker LG, Das M, Abdool Karim Q, et al. Twice-yearly lenacapavir or daily F/TAF for HIV prevention in cisgender women. N Engl J Med. Published online July 24, 2024. doi:10.1056/NEJMoa2407001. Accessed November 19, 2024
  11. Kelley CF. Twice-yearly lenacapavir for HIV prevention in cisgender, gay, bisexual, and other men, transgender women, transgender men, and gender-nonbinary people who have sex with partners assigned male at birth: interim analysis results from the PURPOSE 2 study. Slides presented at: HIV Research for Prevention (HIVR4P); October 6-10, 2024; Lima, Peru. Accessed November 19, 2024
  12. Gilead Sciences. A Phase 2, open-label, multicenter, randomized study to evaluate the pharmacokinetics, safety, and acceptability of twice yearly long-acting subcutaneous lenacapavir for pre-exposure prophylaxis in cisgender women in the United States. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 20, 2023. NLM Identifier: NCT06101329. Accessed November 19, 2024
  13. Gilead Sciences. A Phase 2, open-label, multicenter, randomized study to evaluate the pharmacokinetics and safety of twice yearly long-acting subcutaneous lenacapavir for pre-exposure prophylaxis in people who inject drugs. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 20, 2023. NLM Identifier: NCT06101342. Accessed November 19, 2024
  14. Gilead Sciences. A Phase 2, open-label, multicenter, randomized study to evaluate the persistence, safety, acceptability, and pharmacokinetics of twice yearly long-acting subcutaneous lenacapavir for HIV pre-exposure prophylaxis (PrEP) in people who would benefit from PrEP. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 16, 2024. NLM Identifier: NCT06513312. Accessed November 19, 2024

 

Last Reviewed: November 19, 2024