Drugs

Tenofovir Alafenamide

Tenofovir Alafenamide

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 Organization: Gilead Sciences, Inc. (The darunavir/cobicistat/emtricitabine/tenofovir alafenamide fixed-dose combination [FDC] is being developed by Janssen Research & Development, LLC.) Phase of Development:

Tenofovir alafenamide is a component of the FDC darunavir/cobicistat/emtricitabine/tenofovir alafenamide currently being studied in Phase III trials for HIV treatment. An application for marketing approval of this product was submitted to the U.S. Food and Drug Administration (FDA). The emtricitabine/tenofovir alafenamide FDC (brand name: Descovy) is in Phase III development for HIV prevention.

Four tenofovir alafenamide-based FDCs are FDA-approved for HIV treatment: 1) elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (brand name: Genvoya), 2) emtricitabine/rilpivirine/tenofovir alafenamide (brand name: Odefsey), 3) Descovy, and 4) bictegravir/emtricitabine/tenofovir alafenamide (brand name: Biktarvy). As a stand-alone agent, tenofovir alafenamide (brand name: Vemlidy) is FDA-approved for chronic HBV infection treatment.

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 Janssen press release,3 ClinicalTrials.gov,4,5 and Gilead Sciences, Inc. press releases6-10)

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 tenofovir alafenamide?

What is tenofovir alafenamide?

Tenofovir alafenamide is a component of an investigational fixed-dose combination (FDC) drug (darunavir/cobicistat/emtricitabine/tenofovir alafenamide) currently being studied for the treatment of HIV infection.3 (FDC drugs include 2 or more drugs in a single dosage form, such as a capsule or tablet.)

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 also a component of the following FDC drugs that are FDA-approved to treat HIV infection:

As a stand-alone drug, tenofovir alafenamide (brand name: Vemlidy) is FDA-approved to treat chronic hepatitis B infection (HBV).10

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.11

  • 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.11

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.11

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 tenofovir alafenamide?

In what phase of testing is tenofovir alafenamide?

The investigational FDC drug containing tenofovir alafenamide (darunavir/cobicistat/emtricitabine/tenofovir alafenamide) is currently being studied in Phase III clinical trials for the treatment of HIV infection. An application for marketing approval of this drug was sent to FDA in September 2017.3

Descovy, one of the FDA-approved FDC drugs containing tenofovir alafenamide and emtricitabine, is currently being studied in Phase III clinical trials for HIV prevention.5

What are some studies on tenofovir alafenamide?

What are some studies on tenofovir alafenamide?

HIV treatment: darunavir/cobicistat/emtricitabine/tenofovir alafenamide

Study Names: AMBER; NCT02431247
Sponsor: Janssen Sciences Ireland UC
Phase: III
Status: This study is ongoing, but not recruiting participants.
Locations: United States, Belgium, Canada, France, Germany, Poland, Puerto Rico, Russian Federation, Spain, United Kingdom
Participants:

  • Participants are adults with HIV who have never taken HIV medicines before
  • Participants have viral load levels of at least 1,000 copies/mL or more. (Viral load is the amount of HIV in a blood sample.)
  • Participants have CD4 cell counts of 50 cells/mm3 or more. (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.)
  • Based on resistance testing, participants are fully sensitive to darunavir, tenofovir disoproxil fumarate, and emtricitabine.

Purpose: The purpose of this study is to compare the effectiveness of darunavir/cobicistat/emtricitabine/tenofovir alafenamide to darunavir/cobicistat and emtricitabine/tenofovir disoproxil fumarate (two FDC drugs given together) in adults with HIV who have never taken HIV medicines.4


Study Names: EMERALD; NCT02269917
Sponsor: Janssen R&D Ireland
Phase: III
Status: This study is ongoing, but not recruiting participants.
Locations: United States, Belgium, Canada, France, Poland, Puerto Rico, Spain, Sweden, Switzerland, United Kingdom
Participants:
  • Participants are adults with HIV who have been on an ART regimen for the 6 months prior to screening.
  • Participants are virologically suppressed with viral loads less than 50 copies/mL for at least 2 months prior to screening. (Viral suppression is when ART reduces a person’s viral load to an undetectable level.)
  • Participants have no history of virological failure on a darunavir-based regimen and have no documented resistance to darunavir. (Virologic failure is when ART cannot control a person’s viral load.)

Purpose: The purpose of this study is to evaluate the effectiveness of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in virologically suppressed adults who are switched from their current ART regimens to the investigational regimen.12,13


HIV prevention: emtricitabine/tenofovir alafenamide (FTC/TAF; Descovy)

Study Names: DISCOVER; GS-US-412-2055; NCT02842086
Sponsor: Gilead Sciences
Phase: Phase III
Status: This study is ongoing, but not recruiting participants.
Locations: United States, Austria, Canada, Denmark, France, Germany, Ireland, Italy, Netherlands, Spain, United Kingdom
Participants:
  • Participants are men and transgender women (TGW) who have sex with men.
  • Participants do not have HIV but are at high risk of sexual acquisition of HIV.

Purpose: The purpose of this study is to evaluate the safety and effectiveness of emtricitabine/tenofovir alafenamide in preventing HIV infection in men and transgender women who have sex with men and are at high risk of acquiring HIV.5

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

What side effects might tenofovir alafenamide cause?

What side effects might tenofovir alafenamide cause?

One goal of HIV research is to identify new drugs that have fewer side effects. The following side effects were observed in the treatment studies listed above that are investigating an FDC drug containing tenofovir alafenamide.

AMBER (NCT02431247):

In this Phase III study, there were few cases of serious side effects and reports of participants discontinuing the drug due to these side effects. The most commonly reported side effects possibly related to the study drug were diarrhea, rash, and nausea. In terms of the bones and kidneys, darunavir/cobicistat/emtricitabine/tenofovir alafenamide had a better safety profile than the HIV regimen it was compared to; for blood fat levels, it was slightly worse.14,15

EMERALD (NCT02269917):

In this Phase III study, investigators considered only one serious side effect, pancreatitis (inflammation of the pancreas), as possibly related to the study drug. Diarrhea and bone loss (osteopenia ) were the most common drug-related side effects. Darunavir/cobicistat/emtricitabine/tenofovir alafenamide had a better kidney and bone safety profile than the drug regimen it was compared to.13

Other side effect information on tenofovir alafenamide may be found in the following FDA drug labels: Genvoya, Odefsey, Descovy, Vemlidy, and Biktarvy.16-20

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

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

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.

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.11

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. nlm.nih.gov/chemidplus/rn/379270-37-8. Last accessed on April 19, 2018.
  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 April 19, 2018.
  3. Janssen: Press Release, dated September 27, 2017. Janssen submits new drug application to U.S. Food and Drug Administration for the first darunavir-based single tablet regimen for the treatment of HIV-1. Available at: http://www.janssen.com/janssen-submits-new-drug-application-us-food-and-drug-administration-first-darunavir-based-single. Last accessed on April 19, 2018. [Archived at WebCite]
  4. 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 19, 2018.
  5. Gilead Sciences. A Phase 3, randomized, double-blind study to evaluate the safety and efficacy of emtricitabine and tenofovir alafenamide (F/TAF) fixed-dose combination once daily for pre-exposure prophylaxis in men and transgender women who have sex with men and are at risk of HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 20, 2016. NLM Identifier: NCT02842086. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02842086. Last accessed on April 19, 2018.
  6. 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. Available at: 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. Last accessed on April 19, 2018. [Archived at WebCite]
  7. 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 19, 2018.
  8. 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 19, 2018.
  9. 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 19, 2018.
  10. Gilead: Press Release, dated November 10, 2016. U.S. Food and Drug Administration Approves Gilead’s Vemlidy® (Tenofovir Alafenamide) for the Treatment of Chronic Hepatitis B Virus Infection. Available at: http://www.gilead.com/news/press-releases/2016/11/us-food-and-drug-administration-approves-gileads-vemlidy-tenofovir-alafenamide-for-the-treatment-of-chronic-hepatitis-b-virus-infection. Last accessed on April 19, 2018.
  11. 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 April 19, 2018.
  12. 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 19, 2018.
  13. Orkin C, Molina JM, Negredo E, et al. Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non-inferiority trial. Lancet HIV. 2018 Jan;5(1):e23-e34. Available at: http://www.natap.org/2017/IDWeek/PIIS2352301817301790(1).pdf. Last accessed on April 19, 2018. [Archived at WebCite]
  14. Eron J, Orkin C, Gallant J, et al. Week 48 results of AMBER: a Phase 3, randomised, double-blind trial in antiretroviral treatment-naïve HIV-1-infected adults to evaluate the efficacy and safety of the once-daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) versus darunavir/cobicistat plus emtricitabine/tenofovir disoproxil fumarate. European AIDS Conference, October 25-27, 2017; Milan, Italy. Levin: Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2017. Available at: http://www.natap.org/2017/EACS/EACS_30.htm. Last accessed on April 19, 2018. [Archived at WebCite]
  15. Orkin, C. Week 48 results of AMBER: a Phase 3, randomised, double-blind trial in antiretroviral treatment (ART)-naïve HIV-1-infected adults to evaluate the efficacy and safety of the once-daily, single-tablet regimen (STR) of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) versus darunavir/cobicistat (DRV/c) plus emtricitabine/tenofovir disoproxil fumarate (FTC/TDF). Abstract presented at: European AIDS Clinical Society (EACS) Conference; October 25-27, 2017; Milan, Italy. Abstract PS8/2. Available at: http://resourcelibrary.eacs.cyim.com/?mediaId=34867. Last accessed on April 19, 2018.
  16. Gilead Sciences, Inc. Genvoya: Full prescribing information, November 29, 2017. DailyMed. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=34784acf-15ed-4715-b504-eb30430518e9. Last accessed on April 19, 2018. [Archived at WebCite]
  17. Gilead Sciences, Inc. Odefsey:: full prescribing information, August 27, 2017. DailyMed. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ea3b9ec8-e04a-412c-8b3f-e5cbc7e641d5. Last accessed on April 19, 2018. [Archived at WebCite]
  18. Gilead Sciences, Inc. Descovy: full prescribing information, October 6, 2017. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06f66e98-e6ee-4538-9506-6c1282cc14c1. Last accessed on April 19, 2018. [Archived at WebCite]
  19. Gilead Sciences, Inc. Vemlidy: full prescribing information, October 5, 2017. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=72e6b33c-0351-4070-9172-eeaa186c01d2. Last accessed on April 19, 2018. [Archived at WebCite]
  20. Gilead Sciences, Inc. Biktarvy: full prescribing information, February 16, 2018. DailyMed. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=664cb8f0-1f65-441b-b0d9-ba3d798be309. Last accessed on April 19, 2018. [Archived at WebCite]

Last Reviewed: April 19, 2018