An Overview of Tenofovir Alafenamide
April 25, 2018
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 R&D Ireland.)
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.
(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 ClinicalTrials.gov,3-5 and Gilead Sciences, Inc. press releases6-10)
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?
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?
Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.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?
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 tDescovy, the FDC tablet of tenofovir alafenamide and emtricitabine, is currently being studied in Phase III clinical trials for HIV prevention.5
What Are Some Studies On Tenofovir Alafenamide?
HIV Treatment: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide
Study Names: AMBER; NCT02431247
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
Status: This study is ongoing, but not recruiting participants.
Locations: United States, Belgium, Canada, France, Poland, Puerto Rico, Spain, Sweden, Switzerland, United Kingdom
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
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?
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.
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.14,15EMERALD (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?
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?
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.
This article was provided by AIDSinfo. Visit the AIDSinfo website to find out more about their activities and publications.
Add Your Comment:
(Please note: Your name and comment will be public, and may even show up in
Internet search results. Be careful when providing personal information! Before
adding your comment, please read TheBody.com's Comment Policy.)