Drug information

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Pronounce:
Other Names:
744 LA, CAB, CAB LA, GSK-1265744, GSK1265744, GSK744, GSK744 LA, GSK744 LAP, S-265744, S/GSK1265744, cabotegravir LA, cabotegravir long-acting injectable, cabotegravir sodium
Drug Class:
Integrase Inhibitors
Molecular Formula:

C19 H17 F2 N3 O5

Registry Number:
1051375-10-0 (CAS)
Chemical Name:

(3S,11aR)-N-((2,4-difluorophenyl)methyl)-6-hydroxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydrooxazolo(3,2-a)pyrido(1,2-d)pyrazine-8-carboxamide

Chemical Class:
Carbamoyl pyridone
Organization:
ViiV Healthcare
Phase of Development:

Cabotegravir is in Phase 3 development for both HIV treatment and HIV prevention. Patients who do not qualify for or are unable to participate in the Phase 3 clinical studies of cabotegravir for HIV treatment may be able to obtain the drug through an expanded access (also called compassionate use) treatment program. For details on the program, go to ClinicalTrials.gov (NCT03462810).

An application for marketing approval of a long-acting two-drug regimen consisting of cabotegravir and rilpivirine for HIV treatment was submitted to the U.S. Food and Drug Administration (FDA) in April 2019. The submission to FDA also included an application for approval of an oral formulation of cabotegravir.

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 HIV/AIDS (Auckland, N.Z.) article,3 HIV Treatment Bulletin article,4 ClinicalTrials.gov,5 and ViiV Healthcare press release6)

What is cabotegravir?What is cabotegravir?

What is cabotegravir?

Cabotegravir is an investigational drug that is being studied to treat and prevent HIV infection.4Cabotegravir is being studied in two forms: as a tablet taken by mouth (called oral cabotegravir or oral CAB) and as a long-acting (LA) injectable given as a shot (called cabotegravir LA or CAB LA).7,8

Cabotegravir belongs to a group of HIV drugs called integrase inhibitors.2 Integrase inhibitors block an HIV enzyme called integrase. By blocking integrase, integrase inhibitors prevent HIV from multiplying and can reduce the amount of HIV in the body.

Cabotegravir oral tablets and a long-acting injectable two-drug regimen consisting of cabotegravir and rilpivirine for HIV treatment has been approved for use in Canada and is currently under review by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).6,9,10

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

Which clinical trials are studying cabotegravir?Which clinical trials are studying cabotegravir?

Which clinical trials are studying cabotegravir?

Cabotegravir for HIV Treatment

Study Names: ATLAS; NCT02951052
Phase: 3
Status: This study is ongoing, but not recruiting participants.
Locations: Multiple countries, including United States
Purpose: The purpose of this study is to evaluate the safety and effectiveness of switching people with viral suppression on an oral HIV treatment regimen to cabotegravir LA plus rilpivirine LA.11

Study Names: FLAIR; NCT02938520
Phase: 3
Status: This study is ongoing, but not recruiting participants.
Locations: Multiple countries, including United States
Purpose: The purpose of this study is to evaluate the safety and effectiveness of cabotegravir LA plus rilpivirine LA in maintaining viral suppression in adults who switched from a suppressive oral HIV regimen.12

Study Names: LATITUDE; ACTG A5359; NCT03635788
Phase: 3
Status: This study is ongoing, but not recruiting participants.
Locations: United States and Puerto Rico
Purpose: The purpose of this study is to compare the safety and effectiveness of cabotegravir LA plus rilpivirine LA versus oral standard of care ART in adults with a history of poor adherence to ART and poorly controlled HIV.13

Study Names: ATLAS-2M; NCT03299049
Phase: 3b
Status: This study is ongoing, but not recruiting participants.
Locations: Multiple countries, including United States
Purpose: The purpose of this study is to evaluate the safety and effectiveness of cabotegravir LA plus rilpivirine LA when given every 8 weeks or every 4 weeks in adults with HIV who have viral suppression.14

Other studies looking at cabotegravir LA for HIV treatment include the following:

  • MOCHA (NCT03497676): A Phase 1/2 study evaluating the safety, acceptability, tolerability, and pharmacokinetics of oral cabotegravir, cabotegravir LA, and rilpivirine LA in children and adolescents with HIV and viral suppression. This study is ongoing, but not recruiting participants.15
  • ACTG A5357 (NCT03739996): A Phase 2 study evaluating whether cabotegravir LA plus the broadly neutralizing antibody (bNAb) VRC07-523LS can maintain viral suppression in adults with HIV. This study is currently recruiting participants.16
  • NCT04001803 and NCT04399551: Two Phase 3 studies evaluating ways to successfully deliver cabotegravir LA plus rilpivirine LA to patients in the United States and in European countries, respectively. NCT04001803 is ongoing, but not recruiting. See the ClinicalTrials.gov record for the status of NCT04399551.17,18


Cabotegravir for HIV Prevention

Study Names: ECLAIR; NCT02076178
Phase: 2a
Status: This study has been completed.
Location: United States
Purpose: The purpose of this study was to evaluate the safety, tolerability, and acceptability of cabotegravir LA for pre-exposure prophylaxis (PrEP).19,20

Study Names: HPTN 077; NCT02178800
Phase: 2a
Status: This study has been completed.
Locations: United States, Brazil, Malawi, South Africa
Purpose: The purpose of this study was to evaluate the safety, tolerability, and pharmacokinetics of cabotegravir LA in participants without HIV.21

Study Names: HPTN 083; NCT02720094
Phase: 2b/3
Status: See the ClinicalTrials.gov record for this study's status.
Locations: United States, Argentia, Brazil, Peru, South Africa, Thailand, Vietnam
Purpose: The purpose of this study is to compare the safety and effectiveness of cabotegravir LA to oral tenofovir disoproxil fumarate/emtricitabine (Truvada) for PrEP.22

Study Names: HPTN 084; NCT03164564
Phase: 3
Status: This study is currently recruiting participants.
Locations: Botswana, Kenya, Malawi, South Africa, Swaziland, Uganda, Zimbabwe
Purpose: The purpose of this study is to compare the safety and effectiveness of cabotegravir LA to oral Truvada for PrEP.23

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

What side effects might cabotegravir cause?What side effects might cabotegravir cause?

What side effects might cabotegravir 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 cabotegravir listed above.

ATLAS (NCT02951052):

In the ATLAS study, besides injection site reactions, fatigue, fever, headache, and nausea were the most common drug-related side effects with cabotegravir LA plus rilpivirine LA. Most of the drug-related side effects that occurred with LA therapy were mild or moderate and none were serious. Only 3% of participants receiving LA therapy withdrew from the study because of a side effect (unrelated to injection site reactions).24

Injection site reactions were common in the study, but most were mild or moderate in intensity and went away within 7 days. Four participants withdrew from the study because of injection site reactions. The most common injection site reaction among participants receiving LA therapy was injection-site pain.24,25

FLAIR (NCT02938520):

In the FLAIR study, with the exception of injection site reactions, headache and fever were the most common drug-related side effects with cabotegravir LA plus rilpivirine LA. Most of the drug-related side effects reported by participants receiving LA therapy were mild or moderate in intensity. Only 3% of participants receiving LA therapy withdrew from the study because of a side effect (unrelated to injection site reactions). One participant receiving LA therapy had a serious, drug-related side effect—arthritis of the right knee.26

Injection site reactions were common. Injection-site pain was the most common injection site reaction, and led to the withdrawal of two participants from the study. Two additional participants withdrew from the study because of injection intolerability. Most injection site reactions decreased over time, were mild or moderate in intensity, and lasted for about 3 days.26,27

ATLAS-2M (NCT03299049):
In the ATLAS-2M study, side effects were similar for participants receiving cabotegravir LA plus rilpivirine LA every 8 weeks and every 4 weeks. Most of the drug-related side effects that occurred were mild to moderate in intensity. Five participants in the every 8-week dosing group and eight participants in the every 4-week doing group withdrew from the study because of a drug-related side effect. Two participants in the every 8-week group had a serious drug-related side effect – presyncope (a feeling of fainting) and sudden pancreatitis. One participant in the every 4-week group experienced a serious drug-related side effect – allergic reaction.14,28

Most injection site reactions were mild to moderate in intensity and lasted for about 3 days. The most common injection site reaction was injection-site pain. A total of 17 participants withdrew from the study because of injection-related reasons.28

ECLAIR (NCT02076178):
During the oral therapy part of the ECLAIR study, treatment-related side effects were mostly mild to moderate. No serious side effects were reported with oral cabotegravir.29

The majority of participants receiving cabotegravir LA had an injection site reaction. Most of these reactions were mild to moderate in intensity and most were cases of injection-site pain. Among the participants receiving cabotegravir LA, 19% had a serious injection site reaction and four participants withdrew from the study because of injection intolerability. Other injection site reactions reported by participants receiving cabotegravir LA included mild itchiness, nodules/bumps, warmth to the touch, bruising, and hardened tissue.29

HPTN 077 (NCT02178800):

In the HPTN 077 study, ten participants discontinued cabotegravir because of drug-related side effects, including gastrointestinal problems, rash, and neurologic issues. Serious side effects reported by participants taking cabotegravir included vertigo and weakness.30

During the injection phase of the study, the majority of participants receiving cabotegravir LA had side effects that were moderate or higher in intensity. Injection site reactions, most of which were mild to moderate, were common in participants receiving cabotegravir LA. Only one participant discontinued cabotegravir due to an injection site reaction. Two participants receiving cabotegravir LA had a severe injection site reaction, although neither participant stopped cabotegravir LA injections.30

HPTN 083 (NCT02720094)
In the HPTN 083 trial, the majority of participants receiving cabotegravir LA experienced injection site reactions, but most of these reactions were mild or moderate. Only 2.2% of participants receiving cabotegravir LA stopped treatment because of an injection-related side effect. Some other side effects that occurred in participants taking cabotegravir LA included increased blood sugar levels, fever, and common cold.22,31

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

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

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

More information about cabotegravir-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.

ReferencesReferences

References

  1. United States National Library of Medicine. ChemIDplus Advanced: cabotegravir. https://chem.nlm.nih.gov/chemidplus/rn/1051375-10-0. Accessed July 13, 2020
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed July 13, 2020
  3. Whitfield T, Torkington A, van Halsema C. Profile of cabotegravir and its potential in the treatment and prevention of HIV-1 infection: evidence to date. HIVAIDS Auckl NZ. 2016;8:157-164.
  4. Collins S and Clayden P, eds. HIV pipeline 2019: new drugs in development. HIV Treatment Bulletin. 2019 Jul; 20(1) Suppl: 1-10. HIV Treatment Bulletin. http://i-base.info/htb/wp-content/uploads/2019/07/PIPELINE-2019-FINAL-full-version.pdf. Accessed July 13, 2020
  5. ViiV Healthcare. GSK1265744 (Cabotegravir, CAB) for named patient/compassionate use in HIV. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 5, 2018. NLM Identifier: NCT03462810. https://www.clinicaltrials.gov/ct2/show/NCT03462810. Accessed July 13, 2020
  6. ViiV Healthcare: Press Release, dated April 29, 2019. ViiV Healthcare submits New Drug Application to US FDA for the first monthly, injectable, two-drug regimen of cabotegravir and rilpivirine for treatment of HIV. https://www.viivhealthcare.com/en-gb/media/press-releases/2019/april/viiv-healthcare-submits-new-drug-application-to-us-fda-for-the-first-monthly-injectable-two-drug-regimen-of-cabotegravir-and-rilpivirine-for-treatment-of-hiv/. Accessed July 13, 2020
  7. ViiV Healthcare. A Phase IIb, dose ranging study of oral GSK1265744 in combination with nucleoside reverse transcriptase inhibitors for induction of human immunodeficiency virus -1 (HIV-1) virologic suppression followed by an evaluation of maintenance of virologic suppression when oral GSK1265744 is combined with oral rilpivirine in HIV-1 infected, antiretroviral therapy naive adult subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 28, 2012. NLM Identifier: NCT01641809. https://clinicaltrials.gov/ct2/show/NCT01641809. Accessed July 13, 2020
  8. ViiV Healthcare. A Phase IIb study evaluating a long-acting intramuscular regimen of GSK1265744 plus TMC278 for the maintenance of virologic suppression following an induction of virologic suppression on an oral regimen of GSK1265744 plus abacavir/lamivudine in HIV-1 infected, antiretroviral therapy-naive adult subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 17, 2014. NLM Identifier: NCT02120352. https://clinicaltrials.gov/ct2/show/NCT02120352. Accessed July 13, 2020
  9. ViiV Healthcare ULC. Vocabria and Cabenuva: product monograph, March 2020. Health Canada. https://pdf.hres.ca/dpd_pm/00055411.PDF. Accessed July 13, 2020
  10. ViiV Healthcare: press release, dated July 29, 2019. ViiV Healthcare submits regulatory application to European Medicines Agency for investigational cabotegravir to be used in combination with rilpivirine as the first monthly, injectable treatment for HIV. https://viivhealthcare.com/en-gb/media/press-releases/2019/july/viiv-healthcare-submits-regulatory-application-to-european-medic/. Accessed July 13, 2020
  11. ViiV Healthcare. A Phase III, randomized, multicenter, parallel-group, non-inferiority, open-label study evaluating the efficacy, safety, and tolerability of switching to long-acting cabotegravir plus long-acting rilpivirine from current INI- NNRTI-, or PI-based antiretroviral regimen in HIV-1-infected adults who are virologically suppressed. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 15, 2016. NLM Identifier: NCT02951052. https://clinicaltrials.gov/ct2/show/NCT02951052. Accessed July 13, 2020
  12. ViiV Healthcare. A Phase III, randomized, multicenter, parallel-group, open-label study evaluating the efficacy, safety, and tolerability of long-acting intramuscular cabotegravir and rilpivirine for maintenance of virologic suppression following switch from an integrase inhibitor single tablet regimen in HIV-1 infected antiretroviral therapy naive adult participants. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 15, 2016. NLM Identifier: NCT02938520. https://clinicaltrials.gov/ct2/show/NCT02938520. Accessed July 13, 2020
  13. National Institute of Allergy and Infectious Diseases. A Phase III study to evaluate long-acting antiretroviral therapy in non-adherent HIV-infected individuals. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 15, 2018. NLM Identifier: NCT03635788. https://clinicaltrials.gov/ct2/show/NCT03635788. Accessed July 13, 2020
  14. ViiV Healthcare. A Phase IIIb, randomized, multicenter, parallel-group, non-inferiority, open-label study evaluating the efficacy, safety, and tolerability of long-acting cabotegravir plus long-acting rilpivirine administered every 8 weeks or every 4 weeks in HIV-1-infected adults who are virologically suppressed. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 2, 2017. NLM Identifier: NCT03299049. https://clinicaltrials.gov/ct2/show/NCT03299049. Accessed July 13, 2020
  15. National Institute of Allergy and Infectious Diseases (NIAID). Phase I/II study of the safety, acceptability, tolerability, and pharmacokinetics of oral and long-acting injectable cabotegravir and long-acting injectable rilpivirine in virologically suppressed HIV-infected children and adolescents. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 6, 2018. NLM Identifier: NCT03497676. https://clinicaltrials.gov/ct2/show/NCT03497676. Accessed July 13, 2020
  16. National Institute of Allergy and Infectious Diseases (NIAID). A study of long-acting cabotegravir plus VRC01LS to maintain viral suppression in adults living with HIV-1. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 9, 2018. NLM Identifier: NCT03739996. https://clinicaltrials.gov/ct2/show/NCT03739996. Accessed July 13, 2020
  17. ViiV Healthcare. A qualitative hybrid III implementation study to identify and evaluate strategies for successful implementation of the cabotegravir rilpivirine long-acting injectable regimen in the US. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 10, 2019. NLM Identifier: NCT04001803. Published February 14, 2020. https://clinicaltrials.gov/ct2/show/NCT04001803. Accessed July 13, 2020
  18. ViiV Healthcare. A Phase IIIb, open-label, hybrid type III trial evaluating implementation strategies for long-acting cabotegravir plus long-acting rilpivirine every two months in hiv-1 infected, virologically suppressed adults in select European healthcare settings. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 18, 2020. NLM Identifier: NCT04399551. https://clinicaltrials.gov/ct2/show/NCT04399551. Accessed July 13, 2020
  19. ViiV Healthcare. A Phase IIa study to evaluate the safety, tolerability and acceptability of long acting injections of the HIV integrase inhibitor, GSK1265744, in HIV uninfected men (ECLAIR). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 27, 2014. NLM Identifier: NCT02076178. https://clinicaltrials.gov/ct2/show/NCT02076178. Accessed July 13, 2020
  20. Markowitz M, Frank I, Grant RM, et al. Safety and tolerability of long-acting cabotegravir injections in HIV-uninfected men (ECLAIR): a multicentre, double-blind, randomised, placebo-controlled, phase 2a trial. Lancet HIV. 2017;4(8):e331-e340.
  21. National Institute of Allergy and Infectious Diseases (NIAID). A Phase IIa study to evaluate the safety, tolerability and pharmacokinetics of the investigational injectable HIV integrase inhibitor, GSK1265744, in HIV-uninfected men and women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 27, 2014. NLM Identifier: NCT02178800. https://clinicaltrials.gov/ct2/show/NCT02178800. Accessed July 13, 2020
  22. National Institute of Allergy and Infectious Diseases (NIAID). A Phase 2b/3 double blind safety and efficacy study of injectable cabotegravir compared to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), for pre-exposure prophylaxis in HIV-uninfected cisgender men and transgender women who have sex with men. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 21, 2016. NLM Identifier: NCT02720094. https://clinicaltrials.gov/ct2/show/NCT02720094. Accessed July 13, 2020
  23. National Institute of Allergy and Infectious Diseases (NIAID). A Phase 3 double blind safety and efficacy study of long-acting injectable cabotegravir compared to daily oral TDF/FTC for pre-exposure prophylaxis in HIV-uninfected women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 22, 2017. NLM Identifier: NCT03164564. https://clinicaltrials.gov/ct2/show/NCT03164564. Accessed July 13, 2020
  24. Swindells S. Long-acting cabotegravir rilpivirine as maintenance therapy: ATLAS Week 48 results. Webcast presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 4-7, 2019; Seattle, WA. http://www.croiwebcasts.org/console/player/41308?mediaType = slideVideo&&crd_fl = 0&ssmsrq = 1552603335674&ctms = 5000&csmsrq = 5060. Accessed July 13, 2020
  25. Swindells S, Andrade-Villanueva J-F, Richmond GJ, et al. Long-acting cabotegravir rilpivirine as maintenance therapy: ATLAS Week 48 results. Abstract presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 4-7, 2019; Seattle, WA. Abstract 139. http://www.croiconference.org/sessions/long-acting-cabotegravir-rilpivirine-maintenance-therapy-atlas-week-48-results. Accessed July 13, 2020
  26. Orkin C. Long-acting cabotegravir rilpivirine for HIV maintenance: FLAIR Week 48 results. Webcast presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 4-7, 2019; Seattle, WA. http://www.croiwebcasts.org/console/player/41309?mediaType = slideVideo&&crd_fl = 0&ssmsrq = 1552868268167&ctms = 5000&csmsrq = 5056. Accessed July 13, 2020
  27. Orkin C, Arastéh K, Hernández-Mora MG, et al. Long-acting cabotegravir rilpivirine for HIV maintenance: FLAIR Week 48 results. Abstract presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 4-7, 2019; Seattle, WA. Abstract 140. http://www.croiconference.org/sessions/long-acting-cabotegravir-rilpivirine-hiv-maintenance-flair-week-48-results. Accessed July 13, 2020
  28. Overton ET. Cabotegravir rilpivirine every 2 months is noninferior to monthly: ATLAS-2M study. Webcast presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 8-11, 2020; Boston, MA. http://www.croiwebcasts.org/console/player/44585?mediaType = slideVideo&. Accessed July 13, 2020
  29. Murray M, Markowitz M, Frank I, et al. Satisfaction and acceptability of cabotegravir long-acting injectable suspension for prevention of HIV: Patient perspectives from the ECLAIR trial. HIV Clin Trials. 2018;19:1-10. doi:10.1080/15284336.2018.1511346
  30. Landovitz R, Li S, Grinsztejn B, et al. Safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in low-risk HIV-uninfected women and men HPTN 077. Slides presented at: International AIDS Society (IAS) Conference on HIV Science; July 23-26, 2017; Paris, France. http://programme.ias2017.org/PAGMaterial/PPT/2899_91/IAS2017_Landovitz_Final_072417.pptx. Accessed July 13, 2020
  31. Landovitz R. HPTN 083 final results: pre-exposure prophylaxis containing long-acting injectable cabotegravir is safe and highly effective for cisgender men and transgender women who have sex with men. International AIDS Conference (IAC); July 6-10, 2020. Levin: Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2020. http://www.natap.org/2020/IAC/IAC_28.htm. Accessed July 13, 2020

Last Reviewed: July 13, 2020