Drugs

Bictegravir

Bictegravir

Other Names: BIC, GS-9883, bictegravir sodium Drug Class: Integrase Inhibitors Molecular Formula: C21 H18 F3 N3 O5 Registry Number: 1611493-60-7 (CAS) Chemical Name: 2,5-Methanopyrido(1',2':4,5)pyrazino(2,1-b)(1,3)oxazepine-10-carboxamide, 2,3,4,5,7,9,13,13a-octahydro-8-hydroxy-7,9-dioxo-N-((2,4,6-trifluorophenyl)methyl)-, (2R,5S,13aR)- Organization: Gilead Sciences, Inc. Phase of Development: Bictegravir is a component of the fixed-dose combination product bictegravir/emtricitabine/tenofovir alafenamide (brand name: Biktarvy), which received marketing approval for the treatment of HIV infection by U.S. Food and Drug Administration in February 2018.

It is unclear whether stand-alone bictegravir will be developed, although a Phase II trial of an investigational NRTI (GS-9131) will evaluate GS-9131 plus stand-alone bictegravir and boosted darunavir as an optimized ART regimen.

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 Gilead Sciences press release,3 and HIV Treatment Bulletin article4)

What is bictegravir?

What is bictegravir?

Bictegravir (also known as GS-9883) is an investigational drug that is being studied to treat HIV infection.5,6

Bictegravir belongs to a group of HIV drugs called integrase inhibitors.5,6 Integrase inhibitors block an HIV enzyme, a type of protein, called integrase. By blocking integrase, integrase inhibitors prevent HIV from multiplying and can reduce the amount of HIV in the body.

Bictegravir can be taken once a day and does not require boosting with an additional drug.5,6

In vitro studies have shown that bictegravir may be effective against strains of HIV that are no longer affected by other HIV medicines.5,7,8

Bictegravir is a component of the fixed-dose combination (FDC) tablet Biktarvy, which has been approved by the Food and Drug Administration (FDA) for the treatment of HIV infection.3,9,10

Which clinical trials are studying bictegravir?

Which clinical trials are studying bictegravir?

Bictegravir single-agent tablet

Study Names: GS-US-442-4148; NCT03472326
Phase: II
Status: This study is currently recruiting participants.
Location: Uganda
Purpose: The purpose of this study is to evaluate the effectiveness of GS-9131 as monotherapy in participants who are on an HIV treatment regimen that is not working to control their HIV infection. A secondary objective of the study is to evaluate the effectiveness an HIV treatment regimen that includes GS-9131, bictegravir, darunavir, and ritonavir.11

Bictegravir/emtricitabine/tenofovir alafenamide FDC tablet (Biktarvy)

Biktarvy was FDA-approved in February 2018. Approval was based on supporting data from the following 4 Phase III trials described below.3

Study Names: GS-US-380-1490; NCT02607956
Phase: III
Status: This study is ongoing, but not recruiting participants.
Location: United States, Australia, Belgium, Canada, Dominican Republic, France, Germany, Italy, Puerto Rico, Spain, United Kingdom
Purpose: The purpose of this study is to evaluate the safety and effectiveness of Biktarvy versus dolutegravir plus Descovy in people with HIV who have never taken HIV medicines before.12–14

Study Names: GS-US-380-1489; NCT02607930
Phase: III
Status: This study is ongoing, but not recruiting participants.
Location: United States, Belgium, Canada, Dominican Republic, France, Germany, Italy, Puerto Rico, Spain, United Kingdom
Purpose: The purpose of this study is to compare Biktarvy to the FDA-approved FDC drug abacavir/dolutegravir/lamivudine (brand name: Triumeq) in terms of safety and effectiveness.15,16

Study Names: GS-US-380-1844; NCT02603120
Phase: III
Status: This study is ongoing, but not recruiting participants.
Location: United States, Australia, Belgium, Canada, France, Germany, Italy, Puerto Rico, Spain, United Kingdom
Purpose: The purpose of this study is to evaluate the effectiveness of switching to Biktarvy versus continuing on an HIV treatment regimen consisting of dolutegravir, abacavir and lamivudine in adults whose HIV is not well-controlled by their current HIV medicines.17,18

Study Names: GS-US-380-1878; NCT02603107
Phase: III
Status: This study is ongoing, but not recruiting participants.
Location: United States, Australia, Belgium, Canada, Dominican Republic, France, Germany, Italy, Puerto Rico, Spain, United Kingdom
Purpose: The purpose of this study is to evaluate the effectiveness of switching to Biktarvy versus continuing on a regimen consisting of boosted atazanavir or boosted darunavir plus either emtricitabine/tenofovir DF (Truvada) or abacavir/lamivudine (Epzicom) in adults whose HIV is well-controlled.18,19

For more details on the studies listed above, see the Health Professional version.

Several other planned or ongoing late-stage or post-approval studies evaluating the effectiveness of Biktarvy are listed on ClinicalTrials.gov. Notably, a Phase IV study (NCT03499483) will evaluate the use of Biktarvy for the prevention of HIV infection in adults without HIV after high-risk sexual contact (non-occupational post-exposure prophylaxis).20

What side effects might bictegravir cause?

What side effects might bictegravir 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 bictegravir listed above.

GS-US-380-1490 (NCT02607956):
In this Phase III study, 5 participants receiving Biktarvy stopped the study because of side effects. The most common side effects were headache, diarrhea, nausea, common cold (nasopharyngitis) and fatigue.14

GS-US-380-1489 (NCT02607930):
In this Phase III study, no participants in the Biktarvy group stopped the study because of side effects. The most common side effects were diarrhea, headache, upper respiratory infection and common cold (nasopharyngitis). Side effects related to digestion, nausea, mental health, and sleep were more common in the Triumeq group than in the Biktarvy group.21

GS-US-380-1844 (NCT02603120):
In this Phase III study, 6 participants in the Biktarvy group stopped the study because of stide effects. The most common side effects in the Biktarvy group were upper respiratory tract infection, the common cold (nasopharyngitis), headache, diarrhea and pain in joints (arthralgia). One person experienced a stroke (cerebrovascular accident), which is classified as a drug-related serious side effect.22

GS-US-380-1878 (NCT02603107):
In this Phase III study, side effects were mostly mild or moderate in severity. Two side effects in the Biktarvy group resulted in participants stopping the study and 1 of these (schizophrenia) was considered drug-related. The most common side effects in the Biktarvy group were headache, flatulence, nausea and diarrhea.18

Additional information on side effects known to be associated with bictegravir can be found in the FDA-approved Full Prescribing Information for Biktarvy.

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

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

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

More information about bictegravir-related research studies is available from the AIDSinfo database of ClinicalTrials.gov study summaries. Click on the title of any trial in the list to see the ClinicalTrials.gov trial summary and more information about the study.

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 information, visit NIH Clinical Research Trials and You.

References

References

  1. United States National Library of Medicine. ChemIDplus Advanced: bictegravir. https://chem.nlm.nih.gov/chemidplus/rn/1611493-60-7. Accessed September 27, 2018.
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed September 27, 2018.
  3. Gilead: Press Release, dated February 7, 2018. U.S. Food and Drug Administration approves Gilead’s Biktarvy® (bictegravir, emtricitabine, tenofovir alafenamide) for treatment of HIV-1 infection. http://www.gilead.com/news/press-releases/2018/2/us-food-and-drug-administration-approves-gileads-biktarvy-bictegravir-emtricitabine-tenofovir-alafenamide-for-treatment-of-hiv1-infection. Accessed September 27, 2018.
  4. Collins S and Clayden P. HIV pipeline 2018: new drugs in development. HIV Treatment Bulletin. 2018 Jul; 19(1) Suppl: 1-29. http://i-base.info/htb/wp-content/uploads/2018/07/PIPELINE-2018-full-version.pdf. Accessed September 27, 2018.
  5. White K, Cihlar T, Miller MD. Potent activity of bictegravir (BIC; GS-9883), a novel unboosted HIV-1 integrase strand transfer inhibitor (INSTI), against patient isolates with INSTI-resistance. American Society for Microbiology (ASM) Microbe; June 16-20, 2016; Boston, MA. http://www.natap.org/2016/HIV/062316_02.htm. Accessed September 27, 2018.
  6. Tsiang M, Kan E, Tsai L, et al. Antiviral activity of GS-9883, a potent next generation HIV-1 integrase strand transfer inhibitor. American Society for Microbiology (ASM) Microbe; June 16-20, 2016; Boston, MA. http://www.natap.org/2016/HIV/062016_04.htm. Accessed September 27, 2018.
  7. Jones G, Goldsmith J, Mulato A, et al. GS-9883, a novel HIV-1 integrase strand transfer inhibitor (INSTI) with optimized in vitro resistance profile. American Society for Microbiology (ASM) Microbe; June 16-20, 2016; Boston, MA. Levin: Bictegravir (GS-9883), a novel HIV-1 integrase strand transfer inhibitor (INSTI) with optimized in vitro resistance profile; National AIDS Treatment Advocacy Project (NATAP); HIV Articles; 2016. http://www.natap.org/2016/HIV/062016_03.htm. Accessed September 27, 2018.
  8. Lazerwith S, Cai R, Chen X, et al. Discovery of GS-9883, an HIV-1 integrase strand transfer inhibitor (INSTI) with improved pharmacokinetics and in vitro resistance profile. American Society for Microbiology (ASM) Microbe; June 16-20, 2016; Boston, MA. Levin: Discovery of bictegravir (GS-9883), a novel, unboosted, once-daily HIV-1 integrase strand transfer inhibitor (INSTI) with improved pharmacokinetics and in vitro resistance profile; National AIDS Treatment Advocacy Project (NATAP); HIV Articles; 2016. http://www.natap.org/2016/HIV/062016_05.htm. Accessed September 27, 2018.
  9. White K, Kulkarni R, Willkom M, et al. Pooled week 48 efficacy and baseline resistance: B/F/TAF in treatment-naive patients. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 4-7, 2018; Boston, MA. Poster 532. https://www.croiconference.org/sites/default/files/posters-2018/1430_White_532.pdf. Accessed September 27, 2018.
  10. Andreatta K, Willkom M, Martin R, et al. Resistance analyses of bictegravir/emtricitabine/tenofovir alafenamide switch studies. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 4-7, 2018; Boston, MA. Poster 506. https://www.croiconference.org/sites/default/files/posters-2018/1430_Andreatta_506.pdf. Accessed September 27, 2018.
  11. Gilead Sciences. A Phase 2 study to evaluate the efficacy of GS-9131 functional monotherapy in HIV-1-infected adults failing a nucleos(t)Ide reverse transcriptase inhibitor-containing regimen with nucleos(t)Ide reverse transcriptase inhibitor resistant virus, followed by continued treatment with a GS-9131+bictegravir+darunavir+ritonavir regimen. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 8, 2018. NLM Identifier: NCT03472326. https://clinicaltrials.gov/ct2/show/NCT03472326. Accessed September 27, 2018.
  12. Sax P, Pozniak A, Arribas J. Phase 3 randomized, controlled, clinical trial of bictegravir coformulated with FTC/TAF in a fixed-dose combination vs dolutegravir + FTC/TAF in treatment-naïve HIV-1-positive adults: Week 48 results. International AIDS Society (IAS) Conference on HIV Science; July 23-26, 2017; Paris, France. Levin: Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2017. http://www.natap.org/2017/IAS/IAS_39.htm. Accessed September 27, 2018.
  13. Gilead Sciences. A Phase 3, randomized, double-blind study to evaluate the safety and efficacy of GS-9883/emtricitabine/tenofovir alafenamide versus dolutegravir + emtricitabine/tenofovir alafenamide in HIV-1 infected, antiretroviral treatment-naive adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 10, 2015. NLM Identifier: NCT02607956. https://clinicaltrials.gov/ct2/show/NCT02607956. Accessed September 27, 2018.
  14. Sax PE, Pozniak A, Montes ML, et al. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a randomised, double-blind, multicentre, Phase 3, non-inferiority trial. Lancet. 2017;390(10107):2073-2082. doi:10.1016/S0140-6736(17)32340-1
  15. Gilead Sciences. A Phase 3, randomized, double-blind study to evaluate the safety and efficacy of GS-9883/emtricitabine/tenofovir alafenamide versus abacavir/dolutegravir/lamivudine in HIV-1 infected, antiretroviral treatment-naive adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 10, 2015. NLM Identifier: NCT02607930. https://clinicaltrials.gov/ct2/show/NCT02607930. Accessed September 27, 2018.
  16. Gallant J, Lazzarin A, Mills A. A phase 3 randomized controlled clinical trial of bictegravir in a fixed-dose combination, B/F/TAF, vs DTG/ABC/3TC in treatment-naive adults at Week 48. International AIDS Society (IAS) Conference on HIV Science; July 23-26, 2017; Paris, France. Levin: Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2017. http://www.natap.org/2017/IAS/IAS_06.htm. Accessed September 27, 2018.
  17. Gilead Sciences. A Phase 3, randomized, double-blind study to evaluate the safety and efficacy of switching from a regimen of dolutegravir and ABC/3TC, or a fixed-dose combination (FDC) of ABC/DTG/3TC to a FDC of GS-9883/F/TAF in HIV-1 infected subjects who are virologically suppressed. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 10, 2015. NLM Identifier: NCT02603120. https://clinicaltrials.gov/ct2/show/NCT02603120. Accessed September 27, 2018.
  18. Daar ES, DeJesus E, Ruane P, et al. Efficacy and safety of switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from boosted protease inhibitor-based regimens in virologically suppressed adults with HIV-1: 48 week results of a randomised, open-label, multicentre, Phase 3, non-inferiority trial. Lancet HIV. 2018;5(7):e347-e356. doi:10.1016/S2352-3018(18)30091-2
  19. Gilead Sciences. A Phase 3, randomized, open-label study to evaluate the safety and efficacy of switching from regimens consisting of boosted atazanavir or darunavir plus either emtricitabine/tenofovir or abacavir/lamivudine to GS-9883/emtricitabine/tenofovir alafenamide in virologically suppressed HIV-1 infected adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 10, 2015. NLM Identifier: NCT02603107. https://clinicaltrials.gov/ct2/show/NCT02603107. Accessed September 27, 2018.
  20. Fenway Community Health. A Phase IV open-label evaluation of safety, tolerability, and acceptability of a fixed-dose formulation of bictegravir, emtricitabine/tenofovir alafenamide (B/F/TAF) for non-occupational prophylaxis following potential exposure to HIV-1. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 9, 2018. NLM Identifier: NCT03499483. https://clinicaltrials.gov/ct2/show/NCT03499483. Accessed September 27, 2018.
  21. Gallant J, Lazzarin A, Mills A, et al. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, Phase 3, randomised controlled non-inferiority trial. Lancet. 2017;390(10107):2063-2072. doi:10.1016/S0140-6736(17)32299-7
  22. Molina J-M, Ward D, Brar I, et al. Switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from dolutegravir plus abacavir and lamivudine in virologically suppressed adults with HIV-1: 48 week results of a randomised, double-blind, multicentre, active-controlled, Phase 3, non-inferiority trial. Lancet HIV. 2018;5(7):e357-e365. doi:10.1016/S2352-3018(18)30092-4

Last Reviewed: September 27, 2018