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AIDSinfo Drug Database

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.
Phase of Development: Phase II and III (as part of three different fixed-dose combination [FDC] tablets; one FDC tablet has completed a Phase II study, and two other FDC tablets are in Phase III testing)
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 and ClinicalTrials.gov3)

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.4,5

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).6

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).7

Tenofovir alafenamide is currently being studied as a component of three different investigational fixed-dose combination (FDC) drugs for the treatment of HIV infection. (Fixed-dose combination 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: 

  • elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide8,9
  • darunavir/cobicistat/emtricitabine/tenofovir alafenamide3
  • emtricitabine/tenofovir alafenamide10

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 safe and effective 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

In what phase of testing is tenofovir alafenamide?

Tenofovir alafenamide, as part of three different fixed-dose combination tablets, is currently being studied in Phase II and Phase III clinical trials.2,3

What have recent studies shown about tenofovir alafenamide?

In a 48-week Phase II study (known as GS-US-299-0102), the safety and effectiveness of one of the once-daily, single-tablet, fixed-dose combination drugs containing tenofovir alafenamide (darunavir/cobicistat/emtricitabine/tenofovir alafenamide) was compared to a regimen of medicines given as four daily tablets (cobicistat-boosted darunavir plus emtricitabine/tenofovir disoproxil fumarate). All study participants were HIV-infected adults who had never taken HIV medicines before entering the study (also called treatment-naive). In addition to the assigned study medicines, participants also received placebo tablets so that everyone was taking similar-looking tablets and the same number of tablets daily. (A placebo is an inactive drug that is identical in appearance to the active drug being studied.)3,12,13 

In this study, the single-tablet, fixed-dose combination drug darunavir/cobicistat/emtricitabine/tenofovir alafenamide appeared to be as effective as cobicistat-boosted darunavir plus emtricitabine/tenofovir disoproxil fumarate in reducing viral load (the amount of HIV in a blood sample). In terms of safety, two participants in each group stopped the study early because of a side effect. The tenofovir alafenamide-containing tablet led to fewer bone- and kidney-related side effects among participants than the treatment containing tenofovir disoproxil fumarate.12,13

In a separate 48-week Phase II study (known as GS-US-292-0102), investigators looked at the safety and effectiveness of another once-daily, single-tablet, fixed-dose combination drug that contained tenofovir alafenamide (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide) and compared it to the FDA-approved fixed-dose combination medicine Stribild (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate). All participants were HIV-infected, treatment-naive adults. Participants in each group also received a placebo tablet.14-16
 
In GS-US-292-0102, the single-tablet, fixed-dose combination drug elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide had similar effectiveness as Stribild in reducing viral load after 48 weeks of treatment. In terms of safety, there were no treatment-related serious side effects or study drop-outs because of kidney problems. The tenofovir alafenamide-containing tablet had less unfavorable effects on bone density and kidney function than Stribild.15,16

There are ongoing Phase III studies investigating tenofovir alafenamide as a component of the single-tablet, fixed-dose combination regimen elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide.8,9 In addition, a fixed-dose combination tablet containing tenofovir alafenamide and emtricitabine is also being evaluated in a Phase III study.10

 

What side effects might tenofovir alafenamide cause?

In both studies discussed under the previous question (GS-US-299-0102 and GS-US-292-0102), most side effects were mild to moderate in severity.12,15

In Study GS-US-299-0102, 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. In Study GS-US-292-0102, some side effects that occurred in participants receiving the elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide tablet were nausea, diarrhea, upper respiratory tract infection, fatigue, headache, and cough.13,16

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.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

  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 October 31, 2014.
  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 October 31, 2014.
  3. 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 October 31, 2014.
  4. 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 October 31, 2014.
  5. 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 October 31, 2014.
  6. 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 October 31, 2014.
  7. 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.
  8. Gilead Sciences. A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Versus Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Disoproxil Fumarate in HIV-1 Positive, Antiretroviral Treatment-Naïve Adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 16, 2013. NLM Identifier: NCT01780506. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01780506. Last accessed on October 31, 2014.
  9. Gilead Sciences. A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Versus Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Disoproxil Fumarate in HIV-1 Positive, Antiretroviral Treatment-Naïve Adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 20, 2013. NLM Identifier: NCT01797445. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01797445. Last accessed on October 31, 2014.
  10. Gilead Sciences. A Phase 3, Randomized, Double-Blind, Switch Study to Evaluate F/TAF in HIV-1 Positive Subjects Who Are Virologically Suppressed on Regimens Containing FTC/TDF. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 22, 2014. NLM Identifier: NCT02121795. Available at: http://www.clinicaltrials.gov/ct2/show/NCT02121795. Last accessed on October 31, 2014.
  11. National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: http://nih.gov/health/clinicaltrials/index.htm. Last accessed on October 31, 2014.
  12. 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 October 31, 2014.
  13. 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 October 31, 2014.
  14. Gilead Sciences. A Phase 2, Randomized, Double-Blinded Study of the Safety and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/GS-7340 Single Tablet Regimen Versus Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single Tablet Regimen in HIV 1 Infected, Antiretroviral Treatment-Naive Adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on December 14, 2011. NLM Identifier: NCT01497899. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01497899. Last accessed on October 31, 2014.
  15. Sax P, Brar I, Elion R, et al. 48 Week Study of Tenofovir Alafenamide (TAF) vs. Tenofovir Disoproxil Fumarate (TDF), Each in a Single Tablet Regimen (STR) with Elvitegravir, Cobicistat, and Emtricitabine [E/C/F/TAF vs. E/C/F/TDF] for Initial HIV Treatment. Abstract presented at: 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 10-13, 2013; Denver, CO. Abstract H-1464d. Available at: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=cc7c2e8e-d70c-4d53-b850-d62af2c1fde6&cKey=4b81ee08-365f-4b8a-9e14-76c428c5c9df&mKey=%7b7DD36E88-52C3-4FF1-A5DF-1D00766558B8%7d. Last accessed on October 31, 2014.
  16. Sax P, Brar I, Elion R, et al. 48 Week Study of Tenofovir Alafenamide (TAF) vs. Tenofovir Disoproxil Fumarate (TDF), Each in a Single Tablet Regimen (STR) with Elvitegravir, Cobicistat, and Emtricitabine [E/C/F/TAF vs. E/C/F/TDF] for Initial HIV Treatment. 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 10-13, 2013; Denver, CO. Levin: Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2013. Available at: http://www.natap.org/2013/ICAAC/ICAAC_54.htm. Last accessed on October 31, 2014.

 


Last Reviewed: October 31, 2014

Last Updated: October 31, 2014


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