Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication VEMLIDY is indicated for the treatment of chronic hepatitis B virus (HBV) infection in adults and pediatric patients 6 years of age and older and weighing at least 25 kg with compensated liver disease [see Clinical Studies (14) ] . FDA label
Also known as Tenofovir alafenamide, TAF, Vemlidy®
GS-7340 · 13 trials · 9 indications
Levels of TFV-DP (geometric mean), comparing the drugs TAF to TDF, observed in pregnancy. Note: Observation of daily PrEP dosing spanned 16 weeks in total, including 8 weeks during pregnancy and 8 weeks in postpartum. Once participants had completed their 8 weeks of in-pregnancy observation, observation of therapy was paused until they entered the postpartum phase.
Levels of TFV-DP (geometric mean), comparing the drugs TAF to TDF, observed in postpartum period. Note: Observation of daily PrEP dosing spanned 16 weeks in total, including 8 weeks during pregnancy and 8 weeks in postpartum. Once participants had completed their 8 weeks of in-pregnancy observation, observation of therapy was paused until they entered the postpartum phase.
The percentage of participants with HBV DNA ≥ 20 IU/mL at Week 48 was analyzed using the modified US FDA-defined snapshot algorithm, which included participants who: 1. Had the last available on-treatment HBV DNA ≥ 20 IU/mL in the Week 48 analysis window (from Day 295 to Day 378, inclusive), or 2. Did not have on-treatment HBV DNA data available in the Week 48 analysis window and * Discontinued study drug prior to or in the Week 48 analysis window due to lack of efficacy, or * Discontinued study drug prior to or in the Week 48 analysis window due to reason other than lack of efficacy and had the last available on-treatment HBV DNA ≥ 20 IU/mL
The primary efficacy endpoint was determined by the achievement of HBV DNA \< 29 IU/mL at Week 48.
Functional cure was defined as hepatitis B surface antigen (HBsAg) loss and hepatitis B virus (HBV) deoxyribonucleic acid (DNA) less than the lower limit of quantitation (LLOQ) at follow-up Week 24. LLOQ for HBV DNA CAP/CTM 2.0 is 20 IU/mL. LLOQ for HBV DNA Cobas 6800 is 10 IU/mL. The HBsAg loss was defined as HBsAg changing from positive at baseline to negative at any postbaseline visit. Percentages were rounded off.
The percentage of participants with HBV DNA \< 20 IU/mL at Week 24 was determined by the Missing = Failure (M = F) approach.
Treatment-emergent AEs were defined as: * Any AEs with an onset date on or after the study drug start date and no later than the study drug stop date + 3 days after permanent discontinuation of study drug; * Any AEs with onset date on or after the study drug start date for those who have not permanently discontinued study drug; * Any AEs leading to premature discontinuation of study drug. The most severe graded AE from all tests was counted for each participant.
Graded treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any postbaseline visit, up to and including the date of last dose of study drug + 3 days for participants who permanently discontinued study drug or the last available date in the database snapshot for participants who were on treatment at the time of the analysis. The most severe graded abnormality from all tests was counted for each participant.
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
AUCinf is defined as the concentration of drug extrapolated to infinite time.
Cmax is defined as the maximum concentration of drug.
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Time-weighted average change from baseline through Week 4 (DAVG4) in serum HBV DNA (log10 IU/mL) for GS-7340 8-, 25-, 40 and 120-mg.
| Arm | Type | Description |
|---|---|---|
| TAF arm | EXPERIMENTAL | Fixed dose combination of 200 mg emtricitabine (FTC) and 25 mg tenofovir alafenamide (TAF) delivered under direct observation for 8 weeks during pregnancy and 8 weeks in postpartum period |
| TDF arm | ACTIVE_COMPARATOR | Fixed dose combination of 200 mg emtricitabine (FTC) and 300 mg tenofovir disoproxil fumarate (TDF) delivered under direct observation for 8 weeks during pregnancy and 8 weeks in postpartum period |
| TAF 25 mg | EXPERIMENTAL | Double-blind (DB) phase: TAF 25 mg + TDF placebo for up to 53 weeks. Open-label extension (OLE) phase: TAF 25 mg for up to 52 weeks. |
| TDF 300 mg | ACTIVE_COMPARATOR | DB phase: TDF 300 mg + TAF placebo for up to 50 weeks. OLE phase: TAF 25 mg for up to 52 weeks. |
| Double-Blind TAF | EXPERIMENTAL | Tenofovir alafenamide (Vemlidy®; TAF) 25 mg tablet + tenofovir disoproxil fumarate (Viread®; TDF) placebo tablet once daily for up to 144 weeks (per amendment 3.1). |
| Double-Blind TDF | ACTIVE_COMPARATOR | TDF 300 mg tablet + TAF placebo tablet once daily for up to 144 weeks (per amendment 3.1). |
| Open-label TAF | EXPERIMENTAL | All participants who complete the double-blind period will be eligible to receive open-label TAF until Week 384 of the study. |
| Part 1 Sentinel Cohort (TAF) | EXPERIMENTAL | TAF + their current failing ARV regimen for 10 days in Part 1 |
| Part 1 Randomized Cohort (TAF) | EXPERIMENTAL | Following review of safety and efficacy data from the Sentinel Cohort, participants will be randomized to receive TAF + their current failing ARV regimen for 10 days in Part 1. |
| Part 1 Randomized Cohort (Placebo) | PLACEBO_COMPARATOR | Following review of safety and efficacy data from the Sentinel Cohort, participants will be randomized to receive placebo + their current failing ARV regimen for 10 days in Part 1. |
| Part 2 E/C/F/TAF+ATV | EXPERIMENTAL | Following a 14-day period to confirm eligibility, participants in the Randomized Cohort TAF group with a \> 0.5 log10 decline in HIV-1 RNA and all participants completing the Randomized Cohort Placebo group will receive E/C/F/TAF+ATV for 48 weeks in Part 2. After completion of Part 2, all participants will be eligible to continue to receive E/C/F/TAF plus ATV in the extension phase until E/C/F/TAF becomes commercially available, or until Gilead Sciences terminates development of E/C/F/TAF in the applicable country. |
| Cohort 1: TAF + VIR-2218 + SLGN + Nivolumab | EXPERIMENTAL | Nucleos(t)ide(s) (NUC)-suppressed participants with chronic hepatitis B (CHB) will receive tenofovir alafenamide (TAF) 25 mg orally once daily (QD) for 36 weeks and VIR-2218 200 mg subcutaneously (SC) once every 4 weeks (Q4W) for 24 weeks. From Week 12 onwards, participants will receive selgantolimod (SLGN) 3 mg orally once a week (QW) for 24 weeks and nivolumab 0.3 mg/kg intravenously (IV) Q4W for up to 24 weeks (only up to protocol amendment 2, nivolumab was no longer administered post implementation of protocol amendment 2). Participants who are on TAF treatment will continue TAF treatment over the duration of study follow-up. Participants will be followed up for 48 weeks post treatment. |
| Cohort 2 Group A: VIR-2218 + SLGN + Nivolumab | EXPERIMENTAL | Viremic participants with CHB will receive VIR-2218, 200 mg SC Q4W for 24 weeks. From Week 12 onwards, participants will receive SLGN 3 mg orally QW for 24 weeks and nivolumab 0.3 mg/kg IV Q4W for up to 24 weeks (only up to protocol amendment 2, nivolumab was no longer administered post implementation of protocol amendment 2). Participants who meet the criteria to initiate NUC treatment will receive TAF 25, mg orally, QD during the study. Participants will be followed up for 48 weeks post treatment. |
| Cohort 2 Group B: SLGN + Nivolumab | EXPERIMENTAL | Viremic participants with CHB will receive SLGN 3 mg orally QW for 24 weeks and nivolumab 0.3 mg/kg IV Q4W for up to 24 weeks. . Viremic participants who meet the criteria to initiate NUC treatment will receive TAF 25 mg orally QD during the study. Participants will be followed up for 48 weeks post treatment. All treatments were administered up to protocol amendment 2 and after the implementation of protocol amendment 2, the treatments were discontinued for Cohort 2 Group B based on Sponsor decision. |
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | EXPERIMENTAL | Participants with chronic hepatitis B (CHB) and moderate or severe renal impairment who were virologically suppressed and taking tenofovir disoproxil fumarate (TDF), a TDF-containing anti-hepatitis B virus (HBV) regimen, or other oral antivirals (OAVs), will switch to tenofovir alafenamide (TAF) and receive TAF 25 milligram (mg) tablet once daily orally for 96 weeks. |
| Part A (Renal Impairment): End Stage Renal Disease | EXPERIMENTAL | Participants with CHB and end stage renal disease who were virologically suppressed and taking TDF, a TDF-containing anti-HBV regimen, or OAVs, will switch to TAF and receive TAF 25 mg tablet once daily orally for 96 weeks. |
| Part B: Hepatic Impairment | EXPERIMENTAL | Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and taking TDF, a TDF-containing anti-HBV regimen, or OAVs, will switch to TAF and receive TAF 25 mg tablet once daily orally for 96 weeks. |
| TAF (Cohort 1) | EXPERIMENTAL | Participants (12 to \< 18 years) weighing ≥ 35 kg will receive TAF 25 mg tablet for 24 weeks |
| Placebo (Cohort 1) | PLACEBO_COMPARATOR | Participants (12 to \< 18 years) weighing ≥ 35 kg will receive placebo tablet for 24 weeks |
| TAF (Cohort 2 Group 1) | EXPERIMENTAL | Participants (6 to \< 12 years) weighing ≥ 25 kg will receive TAF 25 mg tablet for 24 weeks |
| TAF (Cohort 2 Group 2) | EXPERIMENTAL | Participants (6 to \< 12 years) weighing ≥ 14 kg to \< 25 kg will receive TAF 15 mg oral granules for 24 weeks |
| TAF (Cohort 2 Group 3) | EXPERIMENTAL | Participants (2 to \< 6 years) will receive TAF for 24 weeks as follows: * weight ≥ 10 kg to \< 14 kg (7.5 mg oral granules) * weight ≥ 14 kg to \< 25 kg (15 mg oral granules) The study has reopened and recruitment is initiated only for this cohort for ≥ 10 to \< 14 kg at this time. |
| Cohort 2 Placebo | PLACEBO_COMPARATOR | Participants will receive matching placebo of TAF (tablet or oral granules) for 24 weeks. |
| TAF | EXPERIMENTAL | TAF 25 mg once daily for 48 weeks |
| TDF-Containing Regimens | ACTIVE_COMPARATOR | TDF alone or in combination with other approved antivirals per local practice for 48 weeks |
| Optional Treatment Extension Phase | EXPERIMENTAL | After Week 48, participants will be eligible to receive TAF 25 mg once daily for an additional 144 weeks. |
| Severe Hepatic Impairment Group | EXPERIMENTAL | Participants with severe hepatic impairment will receive a single oral dose of TAF 25 mg on Day 1. |
| Matched Normal Hepatic Function Group | ACTIVE_COMPARATOR | Participants with normal hepatic function will receive a single oral dose of TAF 25 mg on Day 1. |
| GS-7340 8mg | EXPERIMENTAL | After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days. |
| GS-7340 25mg | EXPERIMENTAL | After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days. |
| GS-7340 40mg | EXPERIMENTAL | After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days. |
| GS-7340 120mg | EXPERIMENTAL | After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days. |
| Tenofovir disoproxil fumarate 300mg | EXPERIMENTAL | After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days. |
| Name | Type | Description |
|---|---|---|
| Tenofovir alafenamide | DRUG | Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 25 mg tenofovir alafenamide (TAF) |
| Tenofovir Disoproxil Fumarate | DRUG | Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 300 mg tenofovir disoproxil fumarate (TDF) |
| TAF | DRUG | 25 mg tablet administered orally once daily |
| TDF | DRUG | 300 mg tablet administered orally once daily |
| TAF Placebo | DRUG | Tablet administered orally once daily |
| TDF Placebo | DRUG | Tablet administered orally once daily |
| Placebo | DRUG | Tablets to match TAF administered orally once daily with food |
| E/C/F/TAF | DRUG | 150/150/200/10 mg STR administered orally once daily with food |
| Current failing ARV regimen | DRUG | Participants will continue taking their current ARV regimen as prescribed in Part 1. |
| ATV | DRUG | 300 mg tablet administered orally once daily. |
| VIR-2218 | DRUG | Administered as a sub-cutaneous (SC) injection |
| Nivolumab | DRUG | Administered intravenously |
| Selgantolimod | DRUG | Administered as film-coated oral tablets |
| Other approved antivirals | DRUG | Other approved antivirals (such as lamivudine, entecavir, or immunoglobulin antihepatitis B) administered per local practice |
| GS-7340 | DRUG | Subjects are randomized to receive one of four different doses of GS-7340 over 28 days of therapy. |
Inclusion Criteria: 1. \>18 years old 2. confirmed HIV-negative (confirmed with a 4th generation antigen HIV test) at time of study entry 3. intend on giving birth in the MOU facility 4. confirmed to be 14-24 weeks pregnant 5. without psychiatric or medical contraindications to PrEP 6. estimated cr...
GS-7340 is an investigational small molecule developed by Gilead Sciences, Inc. for the treatment of chronic hepatitis B. It has been studied in a Phase 1b clinical trial in treatment-naive adults with the condition. GS-7340 is not approved and remains in clinical development.
GS-7340 is being developed for the treatment of chronic hepatitis B, a viral infection of the liver. Its clinical testing has focused on treatment-naive adults, meaning patients who have not previously received therapy for the condition. The program remains investigational.
GS-7340 is developed by Gilead Sciences, Inc., which trades on the Nasdaq under the ticker GILD. Gilead is the sponsor of the clinical program evaluating the compound in chronic hepatitis B.
GS-7340 is in Phase 1 development. One Phase 1b trial has been completed, and no active trials are currently listed. The compound is investigational and has not been approved for any indication.
GS-7340 has been evaluated in one completed Phase 1b trial, NCT01671787, titled a study assessing GS-7340 in treatment-naive adults with chronic hepatitis B. The randomized, controlled trial enrolled 51 patients across the United States, Australia, Canada, New Zealand, and the United Kingdom.