An Overview of GS-7340

Other Names: Prodrug of tenofovir
Drug Class: Nucleoside Reverse Transcriptase Inhibitors

What is GS-7340?

GS-7340 is an investigational drug for the treatment of HIV infection. It is also being studied in HIV-uninfected participants for use in the treatment of chronic hepatitis B.

• GS-7340 is an investigational anti-HIV drug included in the nucleoside reverse transcriptase inhibitor (NRTI) drug class.
• NRTIs prevent HIV from replicating by blocking reverse transcriptase, an HIV enzyme. By preventing HIV from replicating, NRTIs lower the amount of HIV in the blood.
• GS-7340 is called a prodrug. A prodrug is an inactive drug that is converted inside the body into an active form. In the body, GS-7340 is first converted to tenofovir, which is then converted to an active form of the drug and is called tenofovir diphosphate (TFV-DP) at that point.
• Compared with the FDA-approved NRTI tenofovir disoproxil fumarate (TDF; brand name: Viread), GS-7340 has been shown to deliver higher concentrations of TFV-DP inside certain cells, with lower amounts of tenofovir in the blood. This may translate to greater antiviral activity and fewer side effects with use of GS-7340 than with use of TDF.
• GS-7340 is currently being studied as a component of two investigational fixed-dose combination (FDC) drugs for the treatment of HIV infection:
  • elvitegravir/cobicistat/emtricitabine/GS-7340
  • darunavir/cobicistat/emtricitabine/GS-7340

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.

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.

• 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.

An investigational drug must be proven safe and effective in a Phase III clinical trial to be considered for traditional approval by the FDA for sale in the United States. Some drugs go through the FDA's accelerated approval process and are approved before a Phase III clinical trial is complete. After a drug is approved by the 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.

In what phase of testing is GS-7340?

GS-7340, as part of fixed-dose combination tablets, is currently being studied in Phase II clinical trials.

What have recent studies shown about GS-7340?

In a recent early-phase study, three different doses of GS-7340 taken once daily were compared with placebo and with TDF (given at the standard dose) in HIV-infected participants. Study participants did not receive additional anti-HIV drugs as part of their background regimens. (A background regimen is a combination of drugs that are not being studied as the investigational drug[s] in the clinical trial, but are being given to help control a participant's HIV infection.)

In HIV treatment-naive and treatment-experienced adults, GS-7340 (at the two higher doses studied: 25 mg and 40 mg) proved more effective than TDF at lowering viral load. In this study, GS-7340 resulted in higher TFV-DP levels inside cells and lower tenofovir concentrations in the blood than TDF did. In terms of safety, there were no reports of significant laboratory abnormalities or serious side effects related to GS-7340 use.

Additional Phase II trials involving GS-7340, as part of fixed-dose combination tablets, are under way in treatment-naive adults.

More information on testing of GS-7340 is available from these sources:

• GS-7340 study results presented at the 19^th Conference on Retroviruses and Opportunistic Infections, March 5-8, 2012:
  • 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
• GS-7340 study results presented at the 18^th Conference on Retroviruses and Opportunistic Infections, February 27-March 2, 2011:
  • Markowitz M, Zolopa A, Ruane P, et al. GS-7340 Demonstrates Greater Declines in HIV-1 RNA than TDF during 14 Days of Monotherapy in HIV-1-infected Subjects
• GS-7340 study results presented at the 52^nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 9-12, 2012:
  • Callebaut C, Margot N, Stepan G, et al. Virological Profiling of GS-7340, a Next-generation Tenofovir Prodrug with Superior Potency over TDF
• Studies of fixed-dose combination tablets containing GS-7340 from ClinicalTrials.gov:
  • 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
  • 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

Where can I get more information about clinical trials studying GS-7340?

More information about GS-7340-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 GS-7340. How can I find more information about participating in a clinical trial of an investigational drug?

Clinical trials involve benefits and risks. Before deciding to participate in a clinical trial, talk to your health care provider. For more information on participating in clinical trials, visit NIH Clinical Research Trials and You.