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AIDSinfo Drug Database

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FDA-approved

Investigational

Tenofovir Alafenamide  Audio icon

Other Names: GS-7340, TAF, TFV alafenamide, prodrug of tenofovir, tenofovir alafenamide fumarate
Drug Class: Nucleoside Reverse Transcriptase Inhibitors
Molecular Formula: C21 H29 N6 O5 P
Registry Number: 379270-37-8 (CAS)
Chemical Name: isopropyl (2S)-2-[[[(1R)-2-(6-aminopurin-9-yl)-1-methyl-ethoxy]methyl-phenoxy-phosphoryl]amino]propanoate
Chemical Class: Purine Nucleotides
Company: Gilead Sciences, Inc. (The darunavir/cobicistat/emtricitabine/tenofovir alafenamide fixed-dose combination [FDC] is being developed by Janssen R&D Ireland.)
Phase of Development:

Two tenofovir alafenamide-containing FDC regimens are in Phase III studies: darunavir/cobicistat/emtricitabine/tenofovir alafenamide and GS-9883/emtricitabine/tenofovir alafenamide.

The following three tenofovir alafenamide-containing FDC tablets are FDA-approved: 1) elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (brand name: Genvoya) was approved in November 2015, 2) emtricitabine/rilpivirine/tenofovir alafenamide (brand name: Odefsey) was approved in March 2016, and 3) emtricitabine/tenofovir alafenamide (brand name: Descovy) was approved in April 2016.

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Chemical Image:
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tenofovir alafenamide
tenofovir alafenamide
Molecular Weight: 476.4711
(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 ClinicalTrials.gov,3,4 and Gilead Sciences, Inc. press releases5-8)

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.

What is tenofovir alafenamide?

Tenofovir alafenamide is an investigational drug that is being studied for the treatment of HIV infection. It is also being studied for the treatment of chronic hepatitis B virus (HBV) infection.9,10

Tenofovir alafenamide belongs to a class (group) of HIV drugs called nucleoside reverse transcriptase inhibitors (NRTIs).2 NRTIs block an HIV enzyme called reverse transcriptase. (An enzyme is a protein that starts or increases the speed of a chemical reaction.) By blocking reverse transcriptase, NRTIs prevent HIV from multiplying and can reduce the amount of HIV in the body.

Tenofovir alafenamide is a prodrug, which means that it is an inactive drug. Once taken, a prodrug does not work until the body converts it into an active form. In the body, tenofovir alafenamide is converted to tenofovir diphosphate (TFV-DP).11

Studies suggest that tenofovir alafenamide may be more effective against HIV and cause fewer side effects than the FDA-approved NRTI tenofovir disoproxil fumarate (brand name: Viread).12

Tenofovir alafenamide is currently being studied as a component of two different investigational fixed-dose combination (FDC) drugs for the treatment of HIV infection. (FDC drugs include two or more drugs in a single dosage form, such as a capsule or tablet.) Tenofovir alafenamide is being studied in the following combinations:    

  • darunavir/cobicistat/emtricitabine/tenofovir alafenamide3
  • GS-9883/emtricitabine/tenofovir alafenamide4

Three FDC tablets are FDA-approved. The first FDC tablet contains elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (brand name: Genvoya) and was approved in November 2015.5 The second FDC tablet contains emtricitabine/rilpivirine/tenofovir alafenamide (brand name: Odefsey) and was approved in March 2016.7 The third FDC tablet contains emtricitabine/tenofovir alafenamide (brand name: Descovy) and was approved in April 2016.8

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.13

  • 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.13

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.13

In what phase of testing is tenofovir alafenamide?

Tenofovir alafenamide, as part of two different fixed-dose combination (FDC) tablets, is currently being studied in Phase III clinical trials.3,4

What are some studies on tenofovir alafenamide?

Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (DRV/COBI/FTC/TAF)
Study Names: GS-US-299-0102; NCT01565850
Phase: II
Location: United States and Puerto Rico 
Participants: HIV-infected, treatment-naive adults
Purpose: The purpose of this study was to look at the safety and effectiveness of darunavir/cobicistat/emtricitabine/tenofovir alafenamide FDC tablet versus cobicistat-boosted darunavir + Truvada over 48 weeks. (Boosting means using an ARV medicine or other drug to increase the effectiveness of another ARV medicine. In this case, cobicistat is used to increase the effectiveness of darunavir.)14-16

For more details on this study, see the Health Professional version.

Two Phase III studies will continue to evaluate the darunavir/cobicistat/emtricitabine/tenofovir alafenamide FDC tablet in treatment-naive participants and in treatment-experienced participants with viral loads suppressed to less than 50 copies/mL.3,17


GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/FTC/TAF)
Four Phase III studies will be looking at an FDC tablet containing GS-9883/emtricitabine/tenofovir alafenamide in treatment-naive participants or in treatment-experienced participants with viral loads suppressed to less than 50 copies/mL. (GS-9883 is an investigational integrase inhibitor that does not require boosting.)4,18-21

What side effects might tenofovir alafenamide cause?

In the Phase II study of a darunavir/cobicistat/emtricitabine/tenofovir alafenamide fixed-dose combination (FDC) tablet discussed under the previous question (GS-US-299-0102), most side effects were mild to moderate in severity. Some side effects that were reported by participants receiving the darunavir/cobicistat/emtricitabine/tenofovir alafenamide tablet included diarrhea, upper respiratory tract infection, fatigue, nausea, and rash.15,16

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

Where can I get more information about clinical trials studying tenofovir alafenamide?

More information about tenofovir alafenamide-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.

I am interested in participating in a clinical trial of tenofovir alafenamide. 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.13

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. United States National Library of Medicine. ChemIDplus Advanced. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/379270-37-8. Last accessed on April 23, 2016.
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: http://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Last accessed on April 23, 2016.
  3. Janssen Sciences Ireland UC. A Phase 3, Randomized, Active-controlled, Double-blind Study to Evaluate Efficacy and Safety of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) Once Daily Fixed Dose Combination Regimen Versus a Regimen Consisting of Darunavir/Cobicistat Fixed Dose Combination Coadministered With Emtricitabine/Tenofovir Disoproxil Fumarate Fixed Dose Combination in Antiretroviral Treatment-naive Human Immunodeficiency Virus Type 1 Infected Subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 27, 2015. NLM Identifier: NCT02431247. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02431247. Last accessed on April 23, 2016.
  4. 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-Naïve Adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 10, 2015. NLM Identifier: NCT02607930. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02607930. Last accessed on April 23, 2016.
  5. Gilead: Press Release, dated November 5, 2015. U.S. Food and Drug Administration Approves Gilead’s Single Tablet Regimen Genvoya® (Elvitegravir, Cobicistat, Emtricitabine and Tenofovir Alafenamide) for Treatment of HIV-1 Infection. Available at: http://www.gilead.com/news/press-releases/2015/11/us-food-and-drug-administration-approves-gileads-single-tablet-regimen-genvoya-elvitegravir-cobicistat-emtricitabine-and-tenofovir-alafenamide-for-treatment-of-hiv1-infection. Last accessed on April 23, 2016.
  6. Gilead: Press Release, dated December 29, 2014. Gilead Announces Amended Agreements With Janssen to Develop and Commercialize Tenofovir Alafenamide-Based Single Tablet Regimens for HIV Treatment. Available at: http://www.gilead.com/news/press-releases/2014/12/gilead-announces-amended-agreements-with-janssen-to-develop-and-commercialize-tenofovir-alafenamidebased-single-tablet-regimens-for-hiv-treatment. Last accessed on April 23, 2016.
  7. Gilead: Press Release, dated March 1, 2016. U.S. Food and Drug Administration Approves Gilead’s Second TAF-Based Single Tablet Regimen Odefsey® (Emtricitabine, Rilpivirine, Tenofovir Alafenamide) for the Treatment of HIV-1 Infection. Available at: http://www.gilead.com/news/press-releases/2016/3/us-food-and-drug-administration-approves-gileads-second-tafbased-single-tablet-regimen-odefsey-emtricitabine-rilpivirine-tenofovir-alafenamide-for-the-treatment-of-hiv1-infection. Last accessed on April 23, 2016.
  8. Gilead: Press Release, dated April 4, 2016. U.S. Food and Drug Administration Approves Descovy® (Emtricitabine, Tenofovir Alafenamide), Gilead’s Third TAF-Based HIV Therapy. Available at: http://www.gilead.com/news/press-releases/2016/4/us-food-and-drug-administration-approves-descovy-emtricitabine-tenofovir-alafenamide-gileads-third-tafbased-hiv-therapy. Last accessed on April 23, 2016.
  9. Gilead Sciences. A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Tenofovir Alafenamide (TAF) 25 mg QD Versus Tenofovir Disoproxil Fumarate (TDF) 300 mg QD for the Treatment of HBeAg Positive, Chronic Hepatitis B. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 20, 2013. NLM Identifier: NCT01940471. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01940471. Last accessed on April 23, 2016.
  10. Gilead Sciences. A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Tenofovir Alafenamide (TAF) 25 mg QD Versus Tenofovir Disoproxil Fumarate (TDF) 300 mg QD for the Treatment of HBeAg-Negative, Chronic Hepatitis B. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 20, 2013. NLM Identifier: NCT01940341. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01940341. Last accessed on April 23, 2016.
  11. García-Lerma JG, Aung W, Cong ME, et al. Natural substrate concentrations can modulate the prophylactic efficacy of nucleotide HIV reverse transcriptase inhibitors. J Virol. 2011 Jul;85(13):6610-7. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126530/. Last accessed on April 23, 2016.
  12. Ruane P, DeJesus E, Berger D, et al. GS-7340 25 mg and 40 mg Demonstrate Superior Efficacy to Tenofovir 300 mg in a 10-day Monotherapy Study of HIV-1+ Patients. Paper presented at: 19th Conference on Retroviruses and Opportunistic Infections (CROI); March 5-8, 2012; Seattle, WA. Paper 103. Available at: http://www.retroconference.org/2012b/Abstracts/44081.htm. Last accessed on May 29, 2013.
  13. National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: http://www.nih.gov/health-information/nih-clinical-research-trials-you. Last accessed on April 23, 2016.
  14. Gilead Sciences. A Phase 2, Randomized, Double-Blinded Study of the Safety and Efficacy of Darunavir/Cobicistat/Emtricitabine/GS-7340 Single Tablet Regimen Versus Cobicistat-boosted Darunavir Plus Emtricitabine/Tenofovir Disoproxil Fumarate Fixed Dose Combination in HIV-1 Infected, Antiretroviral Treatment Naive Adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 27, 2012. NLM Identifier: NCT01565850. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01565850. Last accessed on April 23, 2016.
  15. Mills A, Ortiz R, Crofoot G Jr, et al. 48 Week Study of the First PI-based Single Tablet-Regimen (STR) Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) vs. Cobicistat (COBI)-boosted Darunavir (DRV) and Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) in Treatment-naïve (TN) Adults. Abstract presented at: 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 5-9, 2014; Washington, DC. Abstract H-647c. Available at: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=19dd97cd-1a73-4adc-9cdb-36743946ec6b&cKey=d7994d1a-681e-49f4-ba2f-c2a15513b895&mKey=%7b5D6B1802-E453-486B-BCBB-B11D1182D8BB%7d. Last accessed on April 23, 2016.
  16. Mills A, Ortiz R, Crofoot G Jr, et al. 48 Week Study of the First PI-based Single Tablet-Regimen (STR) Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) vs. Darunavir (DRV) boosted by Cobicistat (COBI) and Emtricitabine/Tenofovir Disoproxil Fumarate (TVD) in HIV-Infected Treatment-Naïve Adults. 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 5-9, 2014; Washington, DC. Levin: Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2014. Available at: http://www.natap.org/2014/ICAAC/ICAAC_07.htm. Last accessed on April 23, 2016.
  17. Janssen R&D Ireland. A Phase 3, Randomized, Active-controlled, Open-label Study to Evaluate the Efficacy, Safety and Tolerability of Switching to a Darunavir/ Cobicistat/ Emtricitabine/ Tenofovir Alafenamide (D/C/F/TAF) Once-daily Single-tablet Regimen Versus Continuing the Current Regimen Consisting of a Boosted Protease Inhibitor (bPI) Combined With Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) in Virologically-suppressed, Human Immunodeficiency Virus Type 1 (HIV-1) Infected Subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 17, 2014. NLM Identifier: NCT02269917. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02269917. Last accessed on April 23, 2016.
  18. 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-Naïve Adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 10, 2015. NLM Identifier: NCT02607956. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02607956. Last accessed on April 23, 2016.
  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. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02603107. Last accessed on April 23, 2016.
  20. 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://www.clinicaltrials.gov/ct2/show/NCT02603120. Last accessed on April 23, 2016.
  21. Gilead website. Pipeline: HIV/AIDS. Available at: http://gilead.com/research/pipeline. Last accessed on April 23, 2016.


Last Reviewed: April 24, 2016

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