CLINICAL TRIALS PROFILE FOR COBICISTAT; ELVITEGRAVIR; EMTRICITABINE; TENOFOVIR ALAFENAMIDE FUMARATE

All Clinical Trials for Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide Fumarate

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01497899 ↗	Safety and Efficacy of E/C/F/TAF (Genvoya®) Versus E/C/F/TDF (Stribild®) in HIV-1 Infected, Antiretroviral Treatment-Naive Adults	Completed	Gilead Sciences	Phase 2	2011-12-28	The primary objective of this study is to evaluate the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (Genvoya®; E/C/F/TAF) fixed-dose combination (FDC) versus elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (Stribild®; E/C/F/TDF) FDC in HIV-1 infected, antiretroviral treatment-naive adults.
NCT01780506 ↗	Study to Evaluate the Safety and Efficacy of E/C/F/TAF (Genvoya®) Versus E/C/F/TDF (Stribild®) in HIV-1 Positive, Antiretroviral Treatment-Naive Adults	Completed	Gilead Sciences	Phase 3	2012-12-26	The primary objective of this study is to evaluate the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) versus elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) FDC in HIV-1 positive, antiretroviral treatment-naive adults.
NCT01797445 ↗	Study to Evaluate the Safety and Efficacy of E/C/F/TAF Versus E/C/F/TDF in HIV-1 Positive, Antiretroviral Treatment-Naive Adults	Completed	Gilead Sciences	Phase 3	2013-03-12	The primary objective of this study is to evaluate the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) versus elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) in HIV-1 positive, antiretroviral treatment-naive adults.
NCT02251236 ↗	Elvitegravir (EVG) Cerebrospinal Fluid (CSF) Pharmacokinetics in HIV-Infected Individuals	Completed	Gilead Sciences	N/A	2016-01-01	The project will have two tracks, one for participants who are currently taking elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate or E/C/F/tenofovir alafenamide (E/C/F/TDF or E/C/F/TAF) single-tablet regimen* (STR) (Track A) and one for participants who will begin therapy with E/C/F/TDF or E/C/F/TAF STR during the study (Track B). Participants will take E/C/F/TDF and/or E/C/F/tenofovir alafenamide fumarate (E/C/F/TAF) STR** (if available) for 24 weeks. *Co-formulation of 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 300 mg of tenofovir disoproxil fumarate. **Co-formulation of 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 10 mg of tenofovir alafenamide fumarate.
NCT02251236 ↗	Elvitegravir (EVG) Cerebrospinal Fluid (CSF) Pharmacokinetics in HIV-Infected Individuals	Completed	University at Buffalo	N/A	2016-01-01	The project will have two tracks, one for participants who are currently taking elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate or E/C/F/tenofovir alafenamide (E/C/F/TDF or E/C/F/TAF) single-tablet regimen* (STR) (Track A) and one for participants who will begin therapy with E/C/F/TDF or E/C/F/TAF STR during the study (Track B). Participants will take E/C/F/TDF and/or E/C/F/tenofovir alafenamide fumarate (E/C/F/TAF) STR** (if available) for 24 weeks. *Co-formulation of 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 300 mg of tenofovir disoproxil fumarate. **Co-formulation of 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 10 mg of tenofovir alafenamide fumarate.
NCT02251236 ↗	Elvitegravir (EVG) Cerebrospinal Fluid (CSF) Pharmacokinetics in HIV-Infected Individuals	Completed	University of California, San Diego	N/A	2016-01-01	The project will have two tracks, one for participants who are currently taking elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate or E/C/F/tenofovir alafenamide (E/C/F/TDF or E/C/F/TAF) single-tablet regimen* (STR) (Track A) and one for participants who will begin therapy with E/C/F/TDF or E/C/F/TAF STR during the study (Track B). Participants will take E/C/F/TDF and/or E/C/F/tenofovir alafenamide fumarate (E/C/F/TAF) STR** (if available) for 24 weeks. *Co-formulation of 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 300 mg of tenofovir disoproxil fumarate. **Co-formulation of 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 10 mg of tenofovir alafenamide fumarate.
NCT02616029 ↗	Study to Evaluate Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Fixed Dose Combination (FDC) in Virologically-Suppressed HIV-1 Infected Adults Harboring the Archived Isolated NRTI Resistance Mutation M184V/M184	Completed	Gilead Sciences	Phase 3	2015-12-17	The primary objective of the study is to evaluate the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) after switching from a stable regimen consisting of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or abacavir/lamivudine (ABC/3TC) plus a third antiretroviral (ARV) agent in participants harboring the archived nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) resistance mutation M184V and/or M184I in human immunodeficiency virus (HIV) -1 reverse transcriptase. This is a two part study. If the rate of virologic failure in Part 1 is deemed acceptable, once the internal data monitoring committee officially completes the interim review, the study will continue to Part 2.

Clinical Trial Conditions for Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide Fumarate

Condition Name

Condition Name for Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide Fumarate
Intervention	Trials
HIV-1 Infection	4
HIV	3
HIV Infections	3
HIV/AIDS	2

Condition MeSH

Condition MeSH for Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide Fumarate
Intervention	Trials
HIV Infections	5
Acquired Immunodeficiency Syndrome	3
Hepatitis	1
Coinfection	1

Clinical Trial Locations for Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide Fumarate

Trials by Country

Trials by Country for Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide Fumarate
Location	Trials
United States	89
Switzerland	7
Canada	7
Italy	5
Spain	4

Trials by US State

Trials by US State for Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide Fumarate
Location	Trials
California	7
Missouri	5
Georgia	5
Florida	5
Washington	4

Clinical Trial Progress for Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide Fumarate

Clinical Trial Phase

Clinical Trial Phase for Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide Fumarate
Clinical Trial Phase	Trials
Phase 3	6
Phase 2	2
Phase 1/Phase 2	1

Clinical Trial Status

Clinical Trial Status for Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide Fumarate
Clinical Trial Phase	Trials
Completed	9
Recruiting	1
Withdrawn	1

Clinical Trial Sponsors for Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide Fumarate

Sponsor Name

Sponsor Name for Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide Fumarate
Sponsor	Trials
Gilead Sciences	10
University at Buffalo	1
University of California, San Diego	1

Sponsor Type

Sponsor Type for Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide Fumarate
Sponsor	Trials
Industry	11
Other	7

Clinical Trials, Market Analysis, and Projections for Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide Fumarate

Introduction

The combination of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide fumarate (E/C/F/TAF), marketed as Genvoya, has been a significant advancement in the treatment of HIV-1 infection. This single-tablet regimen (STR) has shown promising results in clinical trials, offering improved tolerability and safety profiles compared to earlier treatments.

Clinical Trials Overview

Efficacy and Safety

Clinical trials have demonstrated the efficacy and safety of E/C/F/TAF. In treatment-naive patients, E/C/F/TAF was found to be non-inferior to regimens containing tenofovir disoproxil fumarate (TDF), such as elvitegravir/cobicistat/emtricitabine/TDF (E/C/F/TDF)[1][4].

For patients switching from TDF-based regimens, particularly those with efavirenz or boosted protease inhibitors, E/C/F/TAF showed superior outcomes in terms of renal and bone safety. These trials highlighted significant improvements in renal function and bone mineral density (BMD) compared to TDF-containing regimens[1][4].

Post-Exposure Prophylaxis (PEP)

In the context of PEP, studies comparing cobicistat-boosted elvitegravir with ritonavir-boosted lopinavir, both using tenofovir disoproxil fumarate/emtricitabine as the backbone, showed that the elvitegravir/cobicistat regimen had better adherence and tolerance. Patients on the lopinavir/ritonavir regimen had higher rates of PEP non-completion and adverse events[2].

Market Analysis

Market Positioning

E/C/F/TAF has positioned itself as a preferred treatment option for HIV-1 infection due to its favorable safety and efficacy profile. The single-tablet regimen enhances patient adherence, which is crucial for the effective management of HIV.

Competitive Landscape

The HIV treatment market is highly competitive, with several antiretroviral therapies available. However, E/C/F/TAF stands out due to its use of tenofovir alafenamide (TAF), which offers reduced systemic exposure to tenofovir compared to TDF, leading to improved renal and bone safety[1][4].

Regulatory Approvals

E/C/F/TAF has received regulatory approvals for use in treatment-naive adults and adolescents, as well as for those switching from other antiretroviral regimens. The FDA approved E/C/F/TAF based on pivotal Phase 3 trials that demonstrated its non-inferiority to other established regimens[4].

Projections and Future Outlook

Market Growth

The global HIV treatment market is expected to grow, driven by increasing awareness, improved diagnostic techniques, and the development of more effective and safer treatments. E/C/F/TAF is likely to capture a significant share of this market due to its clinical benefits and patient-friendly single-tablet formulation.

Patient Preferences and Adherence

Patient adherence is a critical factor in HIV treatment. The once-daily dosing of E/C/F/TAF, combined with its lower incidence of adverse events, is expected to enhance patient compliance and overall treatment outcomes.

Emerging Trends and Innovations

The HIV treatment landscape is continuously evolving, with a focus on developing treatments that are not only effective but also have minimal side effects. The use of TAF in E/C/F/TAF is a prime example of this trend, and future innovations may further enhance the safety and efficacy of antiretroviral therapies.

Key Safety Considerations

Hepatitis B Virus (HBV) Infection

It is crucial to note that E/C/F/TAF should not be used to treat HBV infection. Patients with HBV may experience a worsening of their condition upon stopping this medication, and regular monitoring is necessary[3].

Drug Interactions

Patients taking E/C/F/TAF should be aware of potential drug interactions, including those with antacids, St. John's Wort, and nonsteroidal anti-inflammatory medications. These interactions can affect the efficacy and safety of the treatment[3].

How the Medicine is Used

Dosage and Administration

E/C/F/TAF is available as a tablet and is typically taken once daily with food. Patients should follow the prescription instructions carefully and maintain regular appointments with their healthcare provider for monitoring[3][5].

Expert Opinion

"Given the clinical data, E/C/F/TAF appears to be a promising option for optimizing the tolerability of combination antiretroviral therapy (cART) in HIV-infected patients. Its improved renal and bone safety profiles make it an attractive choice for both treatment-naive patients and those switching from TDF-based regimens," says Dr. William B. Tauber, a reviewer for the FDA's NDA submission for E/C/F/TAF[4].

Key Takeaways

• Efficacy and Safety: E/C/F/TAF has demonstrated non-inferior efficacy and superior safety compared to TDF-containing regimens.
• Market Positioning: The single-tablet regimen enhances patient adherence and is preferred due to its favorable safety profile.
• Regulatory Approvals: Approved for treatment-naive patients and those switching from other regimens.
• Future Outlook: Expected to capture a significant market share due to clinical benefits and patient-friendly formulation.
• Safety Considerations: Should not be used to treat HBV infection, and patients should be aware of potential drug interactions.

FAQs

Q: What is the primary advantage of using E/C/F/TAF over TDF-containing regimens?

A: The primary advantage is the improved renal and bone safety profile due to the use of tenofovir alafenamide (TAF), which reduces systemic exposure to tenofovir.

Q: Can E/C/F/TAF be used to treat hepatitis B virus (HBV) infection?

A: No, E/C/F/TAF should not be used to treat HBV infection, as it can worsen the condition upon stopping the medication.

Q: How is E/C/F/TAF administered?

A: E/C/F/TAF is taken once daily with food, and patients should follow the prescription instructions carefully.

Q: What are the potential drug interactions with E/C/F/TAF?

A: Potential interactions include those with antacids, St. John's Wort, and nonsteroidal anti-inflammatory medications.

Q: Is E/C/F/TAF suitable for patients with renal impairment?

A: Yes, E/C/F/TAF can be used in patients with mild renal impairment (creatinine clearance of at least 50 mL/min), but careful monitoring is necessary.

Sources

1. Elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide for optimization of cART tolerability in HIV-infected patients. PubMed.
2. Tenofovir disoproxil fumarate/emtricitabine plus ritonavir-boosted lopinavir versus cobicistat-boosted elvitegravir as a single-tablet regimen for HIV-1 post-exposure prophylaxis. Oxford Academic.
3. Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir - MedlinePlus. MedlinePlus.
4. 207561-Elvitegravir--Cobicistat--Emtricitabine--Tenofovir alafenamide-Clinical-PREA.pdf. FDA.
5. Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (oral route). Mayo Clinic.