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

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

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00869557 ↗	Study of the Safety and Efficacy of Stribild Versus Atripla in Human Immunodeficiency Virus, Type 1 (HIV-1) Infected, Antiretroviral Treatment-Naive Adults	Completed	Gilead Sciences	Phase 2	2009-04-01	The objective of this double-blinded, multicenter, randomized, active-controlled study is to evaluate the safety and efficacy of Stribild, a single-tablet regimen (STR) containing fixed doses of elvitegravir (EVG)/GS-9350 (cobicistat; COBI)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/FTC/TDF (Atripla) in HIV-1 infected, antiretroviral treatment-naive adult participants. Stribild offers an alternative STR for patients who are not candidates for non-nucleoside reverse transcriptor (NNRTI)-based STRs. Participants will be randomized in a 2:1 ratio to receive Stribild or Atripla. Randomization will be stratified by HIV-1 RNA level (≤ 100,000 copies/mL or > 100,000 copies/mL) at screening. After Week 48, participants will continue to take their blinded study drug and attend visits every 12 weeks until treatment assignments are unblinded (Week 60), at which point all participants will attend an Unblinding Visit and be given the option to participate in an open-label rollover extension (the extension is scheduled to be open until Stribild becomes commercially available, or until Gilead Sciences elects to terminate the study).
NCT01095796 ↗	Study to Evaluate the Safety and Efficacy of Stribild Versus Atripla in Human Immunodeficiency Virus, Type 1 (HIV-1) Infected, Antiretroviral Treatment-Naive Adults	Completed	Gilead Sciences	Phase 3	2010-03-01	To evaluate the safety and efficacy of Stribild®, a single tablet regimen (STR) containing fixed doses of elvitegravir (EVG)/cobicistat (COBI [GS-9350])/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/FTC/TDF (Atripla®) in HIV-1 infected, antiretroviral treatment-naive adults. Stribild offers an alternative STR for patients who are not candidates for non-nucleoside reverse transcriptor-based STRs.
NCT01106586 ↗	Study to Evaluate the Safety and Efficacy of Stribild Versus Ritonavir-Boosted Atazanavir Plus Truvada in Human Immunodeficiency Virus, Type 1 (HIV-1) Infected, Antiretroviral Treatment-Naive Adults	Completed	Gilead Sciences	Phase 3	2010-04-01	To evaluate the safety and efficacy of Stribild®, a single tablet regimen (STR) containing fixed doses of elvitegravir (EVG)/cobicistat (COBI [GS-9350])/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) versus ritonavir-boosted atazanavir (ATV/r) plus the standard of care nucleoside reverse transcriptase inhibitor (NRTI) backbone FTC/TDF (Truvada®). ATV/r + FTC/TDF was selected as the active comparator for this study as it is a preferred protease inhibitor-based regimen in guidelines for the treatment of HIV-1 infected, antiretroviral treatment-naive adults.
NCT01475838 ↗	Study to Evaluate Switching From Regimens Consisting of a Ritonavir-boosted Protease Inhibitor Plus Emtricitabine/Tenofovir Fixed-Dose Combination to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF Single-Tablet Regimen in Virologically Suppr	Completed	Gilead Sciences	Phase 3	2011-11-01	This study will evaluate the non-inferiority of Stribild® (elvitegravir/cobicistat/ emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF)) single-tablet regimen (STR) relative to regimens consisting of a protease inhibitor (PI) boosted with ritonavir (RTV) plus Truvada® (FTC/TDF) fixed-dose combination in maintaining HIV-1 RNA < 50 copies/mL at Week 48 in virologically suppressed, HIV-1 infected adults. This study will also evaluate the safety, tolerability, and efficacy of the two regimens through 96 weeks of treatment.
NCT01495702 ↗	Study to Evaluate Switching From Regimens Consisting of a Nonnucleoside Reverse Transcriptase Inhibitor Plus Emtricitabine and Tenofovir DF to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF Single-Tablet Regimen in Virologically Suppressed,	Completed	Gilead Sciences	Phase 3	2011-12-01	This study will evaluate the noninferiority of Stribild® (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF)) single-tablet regimen (STR) relative to regimens consisting of a nonnucleoside reverse transcriptase inhibitor (NNRTI) plus Truvada® (FTC/TDF) in maintaining HIV-1 RNA < 50 copies/mL at Week 48 in virologically suppressed, HIV-1 infected adults. This study will also evaluate the safety, tolerability, and efficacy of the two regimens through 96 weeks of treatment.
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.
NCT01533259 ↗	Open-Label Pilot Study to Evaluate Switching From a Regimen Consisting of Raltegravir Plus Emtricitabine/Tenofovir DF Fixed-Dose Combination to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF Single-Tablet Regimen in Virologically Suppressed,	Completed	Gilead Sciences	Phase 3	2012-01-01	This study will evaluate the efficacy of Stribild® (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF)) single-tablet regimen (STR) after switching from a regimen consisting of raltegravir plus Truvada® (FTC/TDF) at baseline in maintaining HIV-1 RNA < 50 copies/mL at Week 12 in virologically suppressed, HIV-1 infected adults. This study will also evaluate the safety, tolerability, and efficacy of Stribild over 24 and 48 weeks of treatment.

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

Condition Name

Condition Name for Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate
Intervention	Trials
HIV Infections	11
HIV	9
Acquired Immunodeficiency Syndrome	6
HIV-1 Infection	5

Condition MeSH

Condition MeSH for Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate
Intervention	Trials
HIV Infections	16
Acquired Immunodeficiency Syndrome	10
Immunologic Deficiency Syndromes	7
Infections	2

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

Trials by Country

Trials by Country for Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate
Location	Trials
United States	213
Canada	16
United Kingdom	12
Switzerland	9
France	9

Trials by US State

Trials by US State for Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate
Location	Trials
California	15
Florida	13
North Carolina	12
District of Columbia	11
Texas	11

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

Clinical Trial Phase

Clinical Trial Phase for Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate
Clinical Trial Phase	Trials
Phase 4	6
Phase 3	13
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate
Clinical Trial Phase	Trials
Completed	23
Unknown status	1
Withdrawn	1

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

Sponsor Name

Sponsor Name for Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate
Sponsor	Trials
Gilead Sciences	23
St Stephens Aids Trust	1
University Hospital Inselspital, Berne	1

Sponsor Type

Sponsor Type for Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate
Sponsor	Trials
Industry	25
Other	14

Cobicistat, Elvitegravir, Emtricitabine, and Tenofovir: A Comprehensive Update

Introduction

The combination drug comprising cobicistat, elvitegravir, emtricitabine, and tenofovir, marketed under the brand names Genvoya and Stribild, has been a significant advancement in the treatment of HIV-1 infection. This article provides an update on the clinical trials, market analysis, and future projections for this drug combination.

Clinical Trials Overview

Phase 3 and Phase 2 Trials

The efficacy of this combination drug has been extensively studied in several clinical trials. Key trials include the phase 3 trials 292-0104 and 292-0111, and the phase 2 trial 292-0102, which compared the fixed-dose combination (FDC) of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) to Stribild (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate, STB) in treatment-naive adults[1].

Switch Trials

A notable switch trial, 292-0109, involved adults who were virologically suppressed on STB and were randomized to either switch to E/C/F/TAF or continue their STB regimen. This trial demonstrated the safety and efficacy of switching to the new formulation without compromising viral suppression[1].

Pediatric Studies

A small, open-label, single-arm study (292-0106) was conducted in pediatric patients aged 12 to 18, providing valuable data on the pharmacokinetics and efficacy of E/C/F/TAF in this population[1].

Efficacy and Safety

Antiviral Efficacy

The combination of elvitegravir, cobicistat, emtricitabine, and tenofovir has shown potent and durable antiretroviral efficacy. In the GS-236-0103 study, this regimen was compared to a ritonavir-boosted atazanavir plus emtricitabine and tenofovir disoproxil fumarate. The results indicated high virological success rates, with CD4 cell counts increasing significantly in both treatment groups[2].

Pharmacokinetics

Pharmacokinetic studies have shown consistent and favorable profiles for all components of the drug. For example, elvitegravir plasma concentrations remained above the protein-binding-adjusted IC95, ensuring effective viral suppression[2].

Safety Profile

While the drug combination is generally well-tolerated, it can cause serious side effects such as kidney problems, lactic acidosis, and liver issues. Monitoring for these adverse effects is crucial during treatment[3].

Market Analysis

Market Position

Genvoya and Stribild have established themselves as leading single-tablet regimens (STRs) in the HIV treatment market. Their convenience, efficacy, and favorable safety profile have made them popular choices among healthcare providers and patients.

Competitors

The HIV treatment market is highly competitive, with other STRs like Biktarvy, Descovy, and Odefsey. However, the unique combination of elvitegravir, cobicistat, emtricitabine, and tenofovir, along with its proven efficacy and safety, maintains a strong market position.

Patient Adherence

Studies have shown that single-tablet regimens like Genvoya and Stribild improve patient adherence due to their simplicity and reduced pill burden. This is particularly important for long-term HIV management[4].

Future Projections

Market Growth

The global HIV treatment market is expected to grow, driven by increasing awareness, improved diagnostic techniques, and the development of more effective treatments. Genvoya and Stribild are likely to remain key players in this market.

Regulatory Approvals

Continued regulatory approvals and updates, such as the switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF), will further solidify the position of these drugs. TAF has been shown to have a more favorable renal and bone safety profile compared to TDF[1].

Emerging Markets

Expansion into emerging markets, particularly in regions with high HIV prevalence, is expected to drive growth. Efforts to improve access to these medications in low- and middle-income countries will be crucial.

Key Takeaways

• Clinical Efficacy: The combination of cobicistat, elvitegravir, emtricitabine, and tenofovir has demonstrated high efficacy in treating HIV-1 infection.
• Safety Profile: While generally well-tolerated, the drug can cause serious side effects that require monitoring.
• Market Position: Genvoya and Stribild are leading STRs in the HIV treatment market due to their convenience and efficacy.
• Future Growth: The market is expected to grow, driven by increasing awareness and the need for effective HIV treatments.

FAQs

Q: What is the primary use of cobicistat, elvitegravir, emtricitabine, and tenofovir?

A: This combination drug is used as a complete regimen for the treatment of HIV-1 infection in adults and children weighing at least 55 pounds (25 kilograms)[3].

Q: What are the potential serious side effects of this drug combination?

A: Serious side effects include kidney problems, lactic acidosis, and liver issues. Patients should be monitored for these adverse effects[3].

Q: How does the switch from TDF to TAF impact the treatment?

A: The switch to TAF has been shown to have a more favorable renal and bone safety profile compared to TDF, making it a preferable option for long-term treatment[1].

Q: Can this drug be used during pregnancy?

A: No, this drug is not recommended during pregnancy due to lower exposures of cobicistat and elvitegravir during the second and third trimesters. Patients who become pregnant during therapy should be switched to an alternative regimen[3].

Q: What is the dosing information for this drug?

A: The usual adult dose is one tablet orally once a day with food. For pediatric patients, the dose is adjusted based on weight, with children weighing at least 25 kilograms receiving one tablet orally once a day with food[3].

Sources

1. FDA: 207561 Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir alafenamide Statistical PREA[1].
2. NATAP: Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection[2].
3. Drugs.com: Cobicistat, elvitegravir, emtricitabine, and tenofovir Uses, Side Effects & Dosage[3].
4. Oxford Academic: Tenofovir disoproxil fumarate/emtricitabine plus ritonavir-boosted lopinavir versus cobicistat-boosted elvitegravir as a single-tablet regimen for HIV post-exposure prophylaxis[4].