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, as part of a fixed-dose combination product containing bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), is in Phase III development. An application for marketing approval of BIC/FTC/TAF for the treatment of HIV infection was submitted to the U.S. Food and Drug Administration in June 2017.

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 Gilead Sciences website,3 and Gilead Sciences press release4)

What is an investigational drug?

What is an investigational drug?

An investigational drug is one that is under study and is not approved by the U.S. Food and Drug Administration (FDA) for sale in the United States. Medical research studies are conducted to evaluate the safety and effectiveness of an investigational drug. These research studies are also called clinical trials. Once an investigational drug has been proven safe and effective in clinical trials, FDA may approve the drug for sale in the United States.

To learn more about investigational drugs, read the AIDSinfo What is an Investigational HIV Drug? fact sheet.

What is bictegravir?

What is bictegravir?

Bictegravir (also known as GS-9883) is an investigational drug that is being studied for the treatment of HIV infection.5,6

Bictegravir belongs to a class (group) of HIV drugs called integrase inhibitors.5,6 Integrase inhibitors block an HIV enzyme called integrase. (An enzyme is a protein that starts or increases the speed of a chemical reaction.) 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 (Boosting involves the use of a second drug to increase the effectiveness of the main [first] drug.)

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 (In vitro refers to studies done in test tubes or other laboratory equipment and not on animals or humans.)

Bictegravir is currently being studied as part of a fixed-dose combination (FDC) drug for the treatment of HIV infection. (FDC drugs include 2 or more drugs in a single dosage form, such as a capsule or tablet.) The FDC drug is a single tablet that includes bictegravir, emtricitabine, and tenofovir alafenamide.7,8

How are clinical trials of investigational drugs conducted?

How are clinical trials of investigational drugs conducted?

Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.9

  • Phase I trials: Researchers test an investigational drug in a small group of people (20–80) for the first time. The purpose is to evaluate its safety and identify side effects.
  • Phase II trials: The investigational drug is administered to a larger group of people (100–300) to determine its effectiveness and to further evaluate its safety.
  • Phase III trials: The investigational drug is administered to large groups of people (1,000–3,000) to confirm its effectiveness, monitor side effects, compare it with standard or equivalent treatments, and collect information that will allow the investigational drug to be used safely.9

In most cases, an investigational drug must be proven effective and must show continued safety in a Phase III clinical trial to be considered for approval by FDA for sale in the United States. Some drugs go through FDA’s accelerated approval process and are approved before a Phase III clinical trial is complete. After a drug is approved by FDA and made available to the public, researchers track its safety in Phase IV trials to seek more information about the drug’s risks, benefits, and optimal use.9

Some clinical trials are categorized as “a” or “b,” such as “Phase Ia” or “Phase IIb.” These different subphases typically mean that a study is researching certain types of information or using a certain type of participant population.

In what phase of testing is bictegravir?

In what phase of testing is bictegravir?

Bictegravir, as part of an FDC tablet, is currently being studied in Phase III clinical trials. An application for marketing approval of the FDC tablet for treating HIV infection was submitted to the U.S. Food and Drug Administration in June 2017.3,4

What are some studies on bictegravir?

What are some studies on bictegravir?

Study Names: GS-US-141-1219; NCT02275065
Sponsor: Gilead Sciences
Phase: Ib
Status: This study has been completed.
Location: United States
Participants:

  • The study involved adults with HIV who had either previously taken HIV medicines or who had never taken HIV medicines before entering the study.
  • Particpants who had taken HIV medicines before had never taken integrase inhibitors and had stopped antiretroviral therapy (ART) for at least 12 weeks before entering the study. (ART is the recommended treatment for HIV infection and involves using a combination of different antiretroviral [ARV] drugs to prevent HIV from multiplying.)
  • All participants had viral load levels (the amount of HIV in a blood sample) between 10,000 copies/mL and 400,000 copies/mL at the start of the study. They also had CD4 counts greater than 200 cells/mm3. (A CD4 count is a laboratory test that measures the number of CD4 cells in a sample of blood and is an important indicator of immune function.)

Purpose: The purpose of this study was to evaluate the safety, effectiveness, and drug properties of different doses of bictegravir.10,11

 

Study Names: GS-US-141-1475; NCT02397694
Sponsor: Gilead Sciences
Phase: II
Status: This study is ongoing, but not recruiting participants.
Location: United States
Participants:

  • Participants are adults with HIV who have never taken HIV medicines or who have taken HIV medicines for 10 days or less before starting the study.
  • Participants have viral load levels of at least 1,000 copies/mL and CD4 counts of at least 200 cells/mm3 before starting the study.

Purpose: The purpose of this study is to compare bictegravir to the FDA-approved integrase inhibitor dolutegravir (brand name: Tivicay) in terms of safety and effectiveness. All participants will receive the FDA-approved FDC drug emtricitabine/tenofovir alafenamide (brand name: Descovy) along with either bictegravir or dolutegravir.12,13

 

Study Names: GS-US-380-1490; NCT02607956
Sponsor: Gilead Sciences
Phase: III
Status: This study is ongoing, but not recruiting participants.
Location: North America, Australia, Europe, Africa
Participants:

  • Participants are adults with HIV who have never taken HIV medicines or who have taken HIV medicines for 10 days or less before starting the study.
  • Participants have viral load levels of at least 500 copies/mL at the start of the study.

Purpose: The purpose of this study is to evaluate the safety and effectiveness of the bictegravir/emtricitabine/tenofovir alafenamide FDC tablet versus dolutegravir plus Descovy.14

 

Study Names: GS-US-380-1489; NCT02607930
Sponsor: Gilead Sciences
Phase: III
Status: This study is ongoing, but not recruiting participants.
Location: North America and Europe
Participants:

  • Participants are adults with HIV who have never taken HIV medicines or who have taken HIV medicines for 10 days or less before starting the study.
  • Participants have viral load levels of at least 500 copies/mL at the start of the study.

Purpose: The purpose of this study is to compare the bictegravir/emtricitabine/tenofovir alafenamide FDC tablet to the FDA-approved FDC drug abacavir/dolutegravir/lamivudine (brand name: Triumeq) in terms of safety and effectiveness.15

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

Three additional Phase III studies (NCT02603120, NCT02652624, and NCT02603107) are evaluating the use of the bictegravir/emtricitabine/tenofovir alafenamide FDC tablet in participants whose viral loads are suppressed by a stable ART regimen. These studies will determine the safety and effectiveness of switching participants to the bictegravir/emtricitabine/tenofovir alafenamide FDC tablet versus continuing their original ART regimen. All 3 studies are ongoing, but not recruiting participants.16-18 A fourth Phase III study (NCT03110380), which is currently recruiting participants, will look at the effectiveness of switching to the bictegravir/emtricitabine/tenofovir alafenamide FDC tablet from an ART regimen of either dolutegravir plus Descovy or dolutegravir plus emtricitabine/tenofovir disoproxil fumarate (brand name: Truvada).19

What side effects might bictegravir cause?

What side effects might bictegravir cause?

In the Phase Ib study (NCT02275065) discussed under the previous question, researchers reported that bictegraivr was well tolerated by participants at all doses. No serious side effects occurred, and no participants stopped taking bictegravir during the study because of a side effect.10,20

In the Phase II study (NCT02397694), 85% of participants in the bictegravir group had side effects, but there were no reports of serious side effects related to treatment through 48 weeks. The most common side effects were diarrhea and nausea. One participant in the bictegraivr group stopped treatment because of hives that were caused by one or more of the study drugs.13

In the first 48 weeks of the Phase III GS-US-380-1490 study (NCT02607956), 5 participants receiving bictegravir stopped the study because of side effects. The most common side effects were headache and diarrhea.21

In the first 48 weeks of the Phase III GS-US-380-1489 study (NCT02607930), no participants in the bictegravir group had stopped the study because of side effects. The most common side effects were diarrhea and headache. Side effects related to digestion, nausea, mental health, and sleep were more common in the Triumeq group than in the bictegravir group.22 

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.

How can I find more information about participating in a clinical trial?

How can I find more information about participating in a clinical trial?

Participating in a clinical trial can provide benefits. For example, a volunteer participant can benefit from new research treatments before they are widely available. Participants also receive regular and careful medical attention from a research team that includes doctors and other health professionals. However, clinical trials may also involve risks of varying degrees, such as unpleasant, serious, or even life-threatening side effects from the treatment being studied.9

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

References

  1. United States National Library of Medicine. ChemIDplus Advanced. Available at: https://chem.sis.nlm.nih.gov/chemidplus/rn/1611493-60-7. Last accessed on September 5, 2017.
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Last accessed on September 5, 2017.
  3. Gilead Sciences website. Pipeline. Available at: http://www.gilead.com/research/pipeline. Last accessed on September 5, 2017.
  4. Gilead Sciences: Press Release, dated June 12, 2017. Gilead submits New Drug Application to U.S. Food and Drug Administration for fixed-dose combination of bictegravir, emtricitabine and tenofovir alafenamide for HIV treatment. Available at: http://www.gilead.com/news/press-releases/2017/6/gilead-submits-new-drug-application-to-us-food-and-drug-administration-for-fixeddose-combination-of-bictegravir-emtricitabine-and-tenofovir-alafenamide-for-hiv-treatment. Last accessed on September 5, 2017.
  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. Levin: National AIDS Treatment Advocacy Project (NATAP); HIV Articles; 2016. Available at: http://www.natap.org/2016/HIV/062316_02.htm. Last accessed on September 5, 2017.
  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. Levin: Antiviral Activity of Bictegravir (GS-9883), a Potent Next Generation HIV-1 Integrase Strand Transfer Inhibitor; National AIDS Treatment Advocacy Project (NATAP); HIV Articles; 2016. Available at: http://www.natap.org/2016/HIV/062016_04.htm. Last accessed on September 5, 2017.
  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. Available at: http://www.natap.org/2016/HIV/062016_03.htm. Last accessed on September 5, 2017.
  8. Lazerwith SE, 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. Available at: http://www.natap.org/2016/HIV/062016_05.htm. Last accessed on September 5, 2017.
  9. National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: https://www.nih.gov/health-information/nih-clinical-research-trials-you. Last accessed on September 5, 2017.
  10. Gilead Sciences. A Phase 1b Randomized, Double-Blinded, Sequential Cohort Placebo-Controlled Study of the Safety, Pharmacokinetics, and Antiviral Activity of GS-9883 in HIV-1 Infected Subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 23, 2014. NLM Identifier: NCT02275065. Available at: https://clinicaltrials.gov/ct2/show/NCT02275065. Last accessed on September 5, 2017.
  11. Gallant J, Thompson M, DeJesus E, et al. Novel Insti Gs-9883 10 Day Monotherapy in Hiv-1-Infected Subjects. American Society for Microbiology (ASM) Microbe; June 16-20, 2016; Boston, MA. Levin: Novel Integrase Strand Transfer Inhibitor Bictegravir 10 Day Monotherapy in HIV-1-Infected Patients; National AIDS Treatment Advocacy Project (NATAP); HIV Articles; 2016. Available at: http://natap.org/2016/HIV/062016_01.htm. Last accessed on September 5, 2017.
  12. Gilead Sciences. A Phase 2, Randomized, Double-Blinded Study of 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 March 20, 2015. NLM Identifier: NCT02397694. Available at: https://clinicaltrials.gov/ct2/show/NCT02397694. Last accessed on September 5, 2017.
  13. Sax PE, DeJesus E, Crofoot G, et al. Bictegravir versus dolutegravir, each with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection: a randomised, double-blind, Phase 2 trial. Lancet HIV. 2017 Apr;4(4):e154-e160. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28219610. Last accessed on September 5, 2017.
  14. 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. Available at: https://clinicaltrials.gov/ct2/show/NCT02607956. Last accessed on September 5, 2017.
  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. Available at: https://clinicaltrials.gov/ct2/show/NCT02607930. Last accessed on September 5, 2017.
  16. 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. Available at: https://clinicaltrials.gov/ct2/show/NCT02603120. Last accessed on September 5, 2017.
  17. Gilead Sciences. A Phase 3, Randomized, Open Label Study to Evaluate the Safety and Efficacy of Switching to a Fixed Dose Combination (FDC) of GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/F/TAF) From Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Alafenamide (E/C/F/TAF), Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate (E/C/F/TDF) or Atazanavir + Ritonavir + Emtricitabine/Tenofovir Disoproxil Fumarate (ATV+RTV+FTC/TDF) in Virologically Suppressed HIV-1 Infected Women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 8, 2016. NLM Identifier: NCT02652624. Available at: https://clinicaltrials.gov/ct2/show/NCT02652624. Last accessed on September 5, 2017.
  18. 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. Available at: https://clinicaltrials.gov/ct2/show/NCT02603107. Last accessed on September 5, 2017.
  19. Gilead Sciences. A Phase 3, randomized, double-blind study to evaluate the safety and efficacy of switching from a regimen of dolutegravir and either emtricitabine/tenofovir alafenamide or emtricitabine/tenofovir disoproxil fumarate to a fixed dose combination of bictegravir/ emtricitabine/tenofovir alafenamide in HIV-1 infected subjects who are virologically suppressed. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 7, 2017. NLM Identifier: NCT03110380. Available at: https://clinicaltrials.gov/ct2/show/NCT03110380. Last accessed on September 5, 2017.
  20. Gallant J, Thompson M, Mills T, et al. Novel Insti Gs-9883 10 Day monotherapy in Hiv-1 infected subjects. Abstract presented at: American Society for Microbiology (ASM) Microbe; June 16-20, 2016; Boston, MA. Abstract 415. Available at: http://files.abstractsonline.com/SUPT/1/4060/AllPosterAbstracts.pdf. Last accessed on September 5, 2017.
  21. Sax PE, Pozniak A, Arribas J, et al. 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. Available at: http://www.natap.org/2017/IAS/IAS_39.htm. Last accessed on September 5, 2017.
  22. Gallant J, Lazzarin A, Mills A, et al. A Phase 3 randomized controlled clinical trial of bictegravir in a fixed dose combination, B/F/TAF, vs DTG/ABC/3TC in treatment-naïve 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. Available at: http://www.natap.org/2017/IAS/IAS_06.htm. Last accessed on September 5, 2017.
 

Last Reviewed: September 5, 2017