Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
E/C/F/TAF · 14 trials · 8 indications
Sustained Virologic Response (SVR12) was defined as HCV RNA \< the lower limit of quantitation (LLOQ) at 12 weeks after stopping LDV/SOF treatment.
The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
The percentage of participants with PVR for HIV-1 RNA cutoff at 50 copies/mL at Week 12 was summarized. PVR was the percentage of participants who did not have a confirmed virologic rebound. Virologic rebound was defined as 2 consecutive HIV-1 RNA values ≥ 50 copies/mL or the last available HIV-1 RNA value ≥ 50 copies/mL during the study followed by premature discontinuation from the study.
Treatment-emergent Adverse Events (TEAE) were defined as AEs with onset dates on or after the study drug start date and no later than 30 days after the permanent discontinuation of the E/C/F/TAF (GEN Phase) study drug or all AEs for participants still on E/C/F/TAF. It also includes the AEs that led to premature discontinuation of E/C/F/TAF study drug. Clinical events and clinically significant laboratory abnormalities were graded according to the GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities. Adverse events were graded as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (life threatening).
The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
The percentage of participants with HBV DNA \< 29 IU/mL at Week 24 was calculated using the missing = failure method.
The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
eGFR is a measurement of the kidney's ability to filter blood.
eGFR is a measurement of the kidney's ability to filter blood. The eGFR\_CKD-EPI,cysC method is adjusted for age and sex.
eGFR is a measurement of the kidney's ability to filter blood. The eGFR\_CKD-EPI,creatinine method is adjusted for age, race, and sex.
The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
The percentage of participants experiencing any treatment-emergent serious adverse event was summarized.
The percentage of participants experiencing any treatment-emergent adverse event was summarized.
AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval).
AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval).
AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval).
AUClast is defined as the concentration of drug from time zero to the last observable concentration, area under the concentration time curve to last observation (AUClast).
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval).
Treatment-emergent adverse events (TEAEs) were defined as any AEs that begin or worsen on or after the start of study drug through 30 days after the last dose of study drug. The severity was graded based on the Gilead Sciences Grading Scale for Severity of Adverse Events. An AE that met one or more of the following outcomes was classified as serious: * Fatal * Life-threatening * Disabling/incapacitating * Results in hospitalization or prolongs a hospital stay * A congenital abnormality * Other important medical events may also be considered serious AEs if they may require medical or surgical intervention to prevent one of the outcomes listed above.
TEAEs were defined as any AEs that begin or worsen on or after the start of study drug through 30 days after the last dose of study drug. The severity was graded based on the Gilead Sciences Grading Scale for Severity of Adverse Events. An AE that met one or more of the following outcomes was classified as serious: * Fatal * Life-threatening * Disabling/incapacitating * Results in hospitalization or prolongs a hospital stay * A congenital abnormality * Other important medical events may also be considered serious AEs if they may require medical or surgical intervention to prevent one of the outcomes listed above.
TEAEs were defined as any AEs that begin or worsen on or after the start of study drug through 30 days after the last dose of study drug. The severity was graded based on the Gilead Sciences Grading Scale for Severity of Adverse Events. An AE that met one or more of the following outcomes was classified as serious: * Fatal * Life-threatening * Disabling/incapacitating * Results in hospitalization or prolongs a hospital stay * A congenital abnormality * Other important medical events may also be considered serious AEs if they may require medical or surgical intervention to prevent one of the outcomes listed above.
| Arm | Type | Description |
|---|---|---|
| E/C/F/TAF + LDV/SOF | EXPERIMENTAL | Part 1: Participants will switch from 2 nucleoside reverse transcriptase inhibitors (NRTI) plus a third agent to E/C/F/TAF. Part 2: After 8 weeks of E/C/F/TAF treatment, the participants maintaining HIV-1 RNA \< 50 copies/mL will start receiving LDV/SOF for 12 weeks and continue their HIV treatment until the end of the study. |
| F/R/TAF + LDV/SOF | EXPERIMENTAL | Part 1: Participants will switch from 2 NRTI plus a third agent to F/R/TAF. Part 2: After 8 weeks of F/R/TAF treatment, the participants maintaining HIV-1 RNA \< 50 copies/mL will start receiving LDV/SOF for 12 weeks and continue their HIV treatment until the end of the study. |
| B/F/TAF | EXPERIMENTAL | Participants will switch to B/F/TAF FDC and receive treatment for 48 weeks. |
| Baseline Regimen | ACTIVE_COMPARATOR | Participants will remain on their baseline regimen of E/C/F/TAF, E/C/F/TDF, or ATV+RTV+FTC/TDF for 48 weeks. |
| Extension Phase | EXPERIMENTAL | Following Week 48, participants in countries where B/F/TAF is not available may have the option to receive B/F/TAF for up to 48 additional weeks. |
| E/C/F/TAF | EXPERIMENTAL | Participants will switch from tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) or 3TC plus a third agent to E/C/F/TAF and will receive treatment for 48 weeks. |
| Remain current regimen | ACTIVE_COMPARATOR | Participants will remain on current TDF and FTC (or FTC/TDF) or 3TC plus continuing third agent. |
| Part 1: E/C/F/TAF | EXPERIMENTAL | Participants with M184V and/or M184I mutations in reverse transcriptase and without any other NRTI resistance mutation switched from their current human immunodeficiency virus (HIV) treatment regimen consisting of FTC/TDF or ABC/3TC plus a third antiretroviral agent to E/C/F/TAF (150/150/200/10 mg) FDC tablet orally once daily for 48 weeks. Allowed third agents include: lopinavir/ritonavir (LPV/r), atazanavir + ritonavir (ATV+RTV), atazanavir+cobicistat (ATV+COBI), darunavir + ritonavir (DRV+RTV), darunavir + cobicistat (DRV+COBI), fosamprenavir + ritonavir (FPV + RTV), saquinavir + ritonavir (SQV + RTV), atazanavir (ATV) (no booster) efavirenz (EFV), rilpivirine (RPV), nevirapine (NVP), etravirine (ETR), raltegravir (RAL) or dolutegravir (DTG). |
| Part 2: E/C/F/TAF | EXPERIMENTAL | Participants with M184V and/or M184I mutations in reverse transcriptase and with or without 1 or 2 TAMs switched from their current HIV treatment regimen consisting of FTC/TDF or ABC/3TC plus a third antiretroviral agent to E/C/F/TAF (150/150/200/10 mg) FDC tablet orally once daily for 48 weeks. Allowed third agents include: LPV/r, ATV+RTV, ATV+COBI, DRV+RTV, DRV+COBI, FPV + RTV, SQV + RTV, ATV (no booster) EFV, RPV, NVP, ETR, RAL or DTG. |
| Open-Label Rollover Extension B/F/TAF | EXPERIMENTAL | At Week 96 or the End of E/C/F/TAF Visit (whichever occurs last), participants will be given the option to receive open-label bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for at least 48 weeks. |
| ABC/3TC+3rd Agent | ACTIVE_COMPARATOR | Participants will maintain prior regimen of ABC/3TC plus a third antiretroviral agent for 24 weeks followed by a delayed switch to E/C/F/TAF FDC. Note: the prior regimen is determined by the participant's clinician (prior to entry into the study) and will consist of one of the third antiretroviral agents listed. |
| HIV treatment-naive and HBV treatment-naive | EXPERIMENTAL | HIV/HBV coinfected participants who are HIV treatment-naive and HBV treatment-naive will receive E/C/F/TAF for 48 weeks. |
| HIV-suppressed | EXPERIMENTAL | HIV/HBV coinfected participants who are HIV-suppressed will receive E/C/F/TAF for 48 weeks. |
| Cohort 1 | EXPERIMENTAL | Participants will receive E/C/F/TAF FDC + DRV once daily with food for 48 weeks. Based on safety and efficacy data from Cohort 1 at Week 4, the participants will be randomized into Cohort 2. The participants in Cohort 1 will continue receiving E/C/F/TAF FDC + DRV through 48 weeks. |
| Cohort 2, Treatment Group 1 | EXPERIMENTAL | Participants will be randomized to receive E/C/F/TAF FDC+DRV once daily with food for 48 weeks. |
| Cohort 2, Treatment Group 2 | ACTIVE_COMPARATOR | Participants will be randomized to continue on their baseline DRV-containing ARV regimen for 48 weeks. |
| Stay on Baseline Treatment Regimen (SBR) | ACTIVE_COMPARATOR | Randomized Phase: Participants stayed on their baseline emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF)-containing regimen E/C/F/TDF; efavirenz (EFV)/FTC/TDF; ritonavir (RTV)-boosted atazanavir (ATV)+FTC/TDF; or cobicistat (COBI-boosted ATV+FTC/TDF) administered according to prescribing information for up to 96 weeks. Extension Phase: After completing 96 weeks of randomized treatment (SBR), all participants will be given the opportunity to receive open-label E/C/F/TAF until it becomes commercially available, or until Gilead elects to terminate the development of E/C/F/TAF. |
| E/C/F/TAF (Double-Blind) | EXPERIMENTAL | E/C/F/TAF plus E/C/F/TDF placebo for 144 weeks After 144 weeks, participants will continue to take their blinded study drug until treatment assignments have been unblinded. |
| E/C/F/TDF (Double-Blind) | ACTIVE_COMPARATOR | E/C/F/TDF plus E/C/F/TAF placebo for 144 weeks After 144 weeks, participants will continue to take their blinded study drug until treatment assignments have been unblinded. |
| Open-Label E/C/F/TAF | EXPERIMENTAL | After the unblinding visit, in countries where E/C/F/TAF is not commercially available, participants (except in UK) who complete 144 weeks of study will be given the option to receive open-label E/C/F/TAF and attend study visits every 12 weeks until it becomes commercially available, or until Gilead terminates the study in that country. |
| E/C/F/TAF (Double-Blind Phase) | EXPERIMENTAL | E/C/F/TAF plus E/C/F/TDF placebo for 144 weeks |
| E/C/F/TDF (Double-Blind Phase) | ACTIVE_COMPARATOR | E/C/F/TDF plus E/C/F/TAF placebo for 144 weeks |
| Open-Label Extension Phase | EXPERIMENTAL | After study unblinding, participants who complete 144 weeks of the study had the option to receive open-label E/C/F/TAF until commercially available, or until Gilead Sciences terminated the study in that country. |
| Cohort 1: Age 12 to < 18 Years and Weight ≥ 35 kg | EXPERIMENTAL | Treatment naive adolescents (12 to \< 18 years of age) living with human immunodeficiency virus (HIV) will receive E/C/F/TAF (150/150/200/10 mg) fixed-dose combination (FDC) once daily for 48 weeks. Participants who complete 48 weeks of study treatment will have the option to receive E/C/F/TAF in an extension phase of the study until: a) the participant turns 18 years old and E/C/F/TAF is commercially available for adults in the country in which the participant is enrolled; b) age-appropriate E/C/F/TAF become commercially available in the country in which the participant is enrolled; or c) Gilead elects to terminate development of E/C/F/TAF in that country. |
| Cohort 2: Age 6 to < 12 Years and Weight ≥ 25 kg | EXPERIMENTAL | Children (6 to \< 12 years of age weighing ≥ 25 kg) with HIV who were virologically suppressed will receive E/C/F/TAF (150/150/200/10 mg) FDC once daily for 48 weeks. Participants who complete 48 weeks of study treatment will have the option to receive E/C/F/TAF in an extension phase of the study until: a) the participant turns 18 years old and E/C/F/TAF is commercially available for adults in the country in which the participant is enrolled; b) age-appropriate E/C/F/TAF become commercially available in the country in which the participant is enrolled; or c) Gilead elects to terminate development of E/C/F/TAF in that country. |
| Cohort 3: Age ≥2 Years and Weight ≥ 14 to <25 kg | EXPERIMENTAL | Children (≥ 2 years of age weighing ≥ 14 to \< 25 kg) with HIV who were virologically suppressed will receive E/C/F/TAF (90/90/120/6 mg) FDC once daily for 48 weeks. Participants who attain a weight of ≥ 25 kg during the course of the study will switch to adult E/C/F/TAF (150/150/200/10 mg) tablets administered orally, once daily with food. Participants who complete 48 weeks of study treatment will have the option to receive E/C/F/TAF in an extension phase of the study until: a) the participant turns 18 years old and E/C/F/TAF is commercially available for adults in the country in which the participant is enrolled; b) age-appropriate E/C/F/TAF became commercially available in the country in which the participant is enrolled; or c) Gilead elects to terminate development of E/C/F/TAF in that country. |
| Name | Type | Description |
|---|---|---|
| E/C/F/TAF | DRUG | 150/150/200/10 mg fixed dose combination (FDC) tablet administered orally once daily |
| F/R/TAF | DRUG | 200/25/25 mg FDC tablet administered orally once daily |
| LDV/SOF | DRUG | 90/400 mg FDC tablet administered orally once daily |
| E/C/F/TDF | DRUG | 150/150/200/300 mg FDC administered orally once daily with food |
| ATV | DRUG | ATV 300 mg capsules administered orally once daily with food |
| RTV | DRUG | RTV 100 mg tablets administered orally once daily with food |
| FTC/TDF | DRUG | 200/300 mg tablet administered orally once daily with food |
| B/F/TAF | DRUG | 50/200/25 mg FDC tablet administered orally once daily without regard to food |
| TDF | DRUG | 300 mg tablet administered orally once daily |
| FTC | DRUG | 200 mg capsule administered orally once daily |
| 3TC | DRUG | Tablet administered orally |
| Third agent | DRUG | Third agent may include one of the following regimens: lopinavir+ritonavir (LPV/r; Kaletra®), atazanavir (ATV; Reyataz®) + ritonavir (RTV; Norvir®), ATV + cobicistat (COBI;Tybost®) (or ATV/COBI FDC), DRV + RTV, darunavir (DRV; Prezista®) + COBI (or DRV/COBI FDC), fosamprenavir (FPV; Lexiva®) + RTV , saquinavir (SQV; Invirase®; Fortovase®) + RTV, efavirenz (EFV;Sustiva®), rilpivirine (RPV;Edurant®), nevirapine (NVP;Viramune®), etravirine (ETR;Intelence®), raltegravir (RAL; Isentress®), elvitegravir (EVG) + COBI, or dolutegravir (DTG;Tivicay®) Drug classes: * Protease inhibitors (PI): LPV/r, ATV, RTV, ATV, DRV, FPV, and SQV * Pharmacokinetic enhancer: COBI * Non-nucleoside reverse transcriptase inhibitors (NNRTI): EFV, RPV, NVP, and ETR * Integrase inhibitors: RAL and DTG |
| ABC/3TC | DRUG | 600/300 mg tablets administered orally once daily |
| Third Antiretroviral Agent | DRUG | Third antiretroviral agents could include one of the following: * ATV+cobicistat (COBI; Tybost®) or ATV/COBI FDC * DRV+COBI or DRV/COBI FDC * darunavir (DRV; Prezista®) + RTV * lopinavir/ritonavir (LPV/r; Kaletra®) * atazanavir (ATV; Reyataz®) + ritonavir (RTV; Norvir®) * efavirenz (EFV; Sustiva®) * etravirine (ETR; Intelence®) * nevirapine (NVP; Viramune®) * rilpivirine (RPV; Edurant®) * dolutegravir (DTG; Tivicay®) * raltegravir (RAL; Isentress®) * fosamprenavir (FPV; Lexiva®) + RTV * saquinavir (SQV; Invirase®) + RTV * ATV (no booster) Drug classes: * Protease inhibitors (PI): LPV/r, ATV, RTV, ATV, DRV, FPV and SQV * Pharmacokinetic enhancer: COBI * Non-nucleoside reverse transcriptase inhibitors (NNRTI): EFV, RPV, NVP, and ETR * Integrase inhibitors: RAL and DTG |
| DRV | DRUG | 800 mg tablet administered orally once daily |
| Baseline DRV- containing ARV regimen | DRUG | Participants will take their baseline DRV- containing ARV regimen as prescribed. |
| EFV/FTC/TDF | DRUG | 600/200/300 mg FDC tablet administered orally once daily |
| COBI | DRUG | 150 mg tablet administered orally once daily |
| E/C/F/TDF Placebo | DRUG | Tablet administered orally once daily |
| E/C/F/TAF Placebo | DRUG | Tablet administered orally once daily |
| E/C/F/TAF (Low Dose) | DRUG | 90/90/120/6 mg STR administered once daily orally with food. |
Key Inclusion Criteria: * Chronic genotype (GT) 1, HCV infected, male and non-pregnant/ non-lactating female individuals, without cirrhosis, treatment-naive or treatment-experienced with interferon (IFN) +/- ribavirin (RBV) +/- HCV protease inhibitor (PI). * Compensated cirrhotic individuals must b...
E/C/F/TAF is an investigational single-tablet regimen being developed for the treatment of HIV-1 infection, including HIV-1 positive patients who are antiretroviral treatment-naive or virologically suppressed. It is also studied in patients with mild to moderate renal impairment and in pediatric populations, including adolescents and children.
E/C/F/TAF is a combination of four antiretroviral agents: elvitegravir, an integrase inhibitor; cobicistat, a pharmacokinetic enhancer; emtricitabine, a nucleoside reverse transcriptase inhibitor; and tenofovir alafenamide, a nucleotide reverse transcriptase inhibitor. Together, they target multiple steps in the HIV-1 replication cycle.
E/C/F/TAF is developed by Gilead Sciences, Inc., a biopharmaceutical company traded on NASDAQ under the ticker GILD. Gilead is conducting clinical trials to evaluate the safety and efficacy of this combination regimen in various HIV-1 infected populations.
E/C/F/TAF is in Phase 2 clinical development. While some completed trials are Phase 3, the overall development program includes Phase 2 studies in adolescents and children. The drug has received FDA designations of Priority Review and Accelerated Approval, but it remains investigational and is not yet approved.
E/C/F/TAF has been studied in six completed clinical trials with a total enrollment of 3,578 participants. Key trials include NCT01780506, a Phase 3 study in treatment-naive adults; NCT01818596, a Phase 3 study in patients with renal impairment; and NCT01854775 and NCT02276612, Phase 2 studies in pediatric populations.
Yes, E/C/F/TAF is the same as Genvoya. The acronym stands for elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide, which are the four components of the single-tablet regimen. Clinical trial titles refer to it as Genvoya, and it is being evaluated for HIV-1 treatment.