Either you have JavaScript disabled or your browser does not support Javascript . To work properly, this page requires JavaScript to be enabled.
How to enable JavaScript in your browser?

Bictegravir/emtricitabine/tenofovir alafenamide - Gilead Sciences

Drug Profile

Bictegravir/emtricitabine/tenofovir alafenamide - Gilead Sciences

Alternative Names: B/F/TAF; BIC/FTC/TAF; Bictegravir/F/TAF; Bictegravir/tenofovir-alafenamide/emtricitabine; Biktarvy; Emtricitabine/bictegravir/tenfovir-alafenamide; Emtricitabine/GS 9883/tenofovir alafenamide; Emtricitabine/tenofovir-alafenamide/GS-9883; Emtricitabine/tenofovir-alafenamine/bictegravir; F/GS 9883/TAF; GS 9883/F/TAF; GS 9883/tenofovir alafenamide/emtricitabine; GS-9883/emtricitabine/tenofovir alafenamide; J05AR20; Tenofovir-alafenamide/bictegravir/emtricitabine; Tenofovir-alafenamide/emtricitabine/bictegravir; Tenofovir-alafenamide/emtricitabine/GS-9883; Tenofovir-alafenamide/GS-9338/emtricitabine

Latest Information Update: 20 Oct 2021

At a glance

  • Originator Gilead Sciences
  • Class Antiretrovirals; Deoxyribonucleosides; Oxazepines; Purines; Pyrazines; Pyridones; Pyrimidine nucleosides; Small molecules
  • Mechanism of Action DNA polymerase beta inhibitors; DNA polymerase gamma inhibitors; DNA polymerase I inhibitors; DNA polymerase II inhibitors; HIV integrase inhibitors; HIV reverse transcriptase inhibitors
  • Orphan Drug Status

    Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.

    No
  • New Molecular Entity No

Highest Development Phases

  • Marketed HIV-1 infections

Most Recent Events

  • 18 Oct 2021 Launched for HIV-1 infections (In adolescents, In children) in USA (PO)
  • 18 Oct 2021 Registered for HIV-1 infections (In adolescents, In children) in USA (PO)
  • 02 Jul 2021 Gilead completes a phase-III clinical trial in HIV-1 infections (Treatment-naive) in the USA, Belgium, Canada, Dominican Republic, France, Germany, Italy, Puerto Rico, Spain, United Kingdom (PO) (NCT02607930) (EudraCT2015-004024-54)

Development Overview

Introduction

A fixed-dose combination product comprising of bictegravir, emtricitabine and tenofovir alafenamide, is developed by Gilead Sciences, for the oral treatment of HIV-1 infections. Bictegravir is a HIV-1 integrase inhibitor, emtricitabine is an inhibitor of HIV-1 reverse transcriptase, DNA polymerases α, β, Ɛ, and mitochondrial DNA polymerase γ, and tenofovir alafenamide, a prodrug of tenofovir, is a mitochondrial DNA polymerase γ inhibitor. The combination product is available as a tablet formulation in the US, Denmark, the Netherlands, Norway, Poland, Canada and the United Kingdom, and is approved in the EU, Iceland, Liechtenstein, Australia, China, Japan, Puerto Rico and Hong Kong. Clinical development is also ongoing in several countries worldwide.

See separate drug profiles for bictegravir [see AdisInsight drug profile 800041516], tenofovir alafenamide [see AdisInsight drug profile 800017062] and emtricitabine [see AdisInsight drug profile 800002479].

Key Development Milestones

Prior to August 2019, Gilead Sciences launched a fixed-dose combination of bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy®; 50mg/200mg/25mg) for the treatment of HIV-1 infection in adults [1] . In July 2018, Health Canada granted a Notice of Compliance for a once-daily single tablet regimen of fixed-dose combination of bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy®; 50mg/200mg/25mg). The approval was supported by positive data from studies 1489, 1490, 1844 and 1878 [see below] [2] .

In October 2021, Gilead Sciences announced that the US FDA approved a new low-dose tablet dosage form of bictegravir 30 mg/emtricitabine 120 mg/tenofovir alafenamide 15 mg tablets (Biktarvy®) for pediatric patients weighing at least 14 kg to less than 25 kg who are virologically suppressed or new to antiretroviral therapy. The approval of this supplemental New Drug Application (sNDA) expands the indication for Biktarvy to include younger children living with HIV-1 infection and will help to close the gap between HIV treatment options available for adults and children. The approval was based on data from cohort 3 of a phase II/III trial (see below) [3] .

In February 2018, the US FDA approved a once-daily single tablet regimen of fixed-dose combination of bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy®; 50mg/200mg/25mg) for the treatment of HIV-1 infection in adults. Gilead, subsequently launched the product in the US. The drug is indicated as a complete regimen for the treatment of HIV-1 infection in adults who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 c/mL) on a stable antiretroviral regimen for at least three months with no history of treatment failure and no known substitutions associated with resistance to the individual components of Biktarvy [4] [5] . In June 2017, Gilead Sciences submitted an NDA to the US FDA for the approval of the fixed-dose combination. The NDA was based on data from four phase III studies which met their primary objective of non-inferiority, including Studies 1489, 1490, 1844 and 1878 [6] . In August 2017, the US FDA granted priority review status to the NDA and assigned 12 February 2018 as the PDUFA date [7] .

In June 2018, the EMA approved the use of Gilead’s bictegravir/emtricitabine/tenofovir alafenamide tablet (Biktarvy®) for the treatment of HIV-1 infections [8] . Earlier in April 2018, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) had issued a positive opinion recommending marketing authorisation for the fixed-dose combination of bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy®; 50mg/200mg/25mg) for the treatment of HIV-1 infection in adults without present or past evidence of viral resistance to the integrase class, emtricitabine or tenofovir. The positive opinion was based on data from the four ongoing phase III studies comprised of 2415 patients [9] .In July 2017, Gilead Sciences submitted an MAA to the EMA for a once-daily single tablet regimen of the fixed-dose combination of bictegravir/emtricitabine/tenofovir alafenamide (50mg/200mg/25mg) for the treatment of treatment-experienced and treatment naive HIV-1 infection in adults. The MAA has been validated by the EMA and is currently under review. The MAA, filed under centralised procedure, was based on data from four phase III studies in which the regimen met the primary objective of non-inferiority [10] .

In August 2019, the China National Medical Products Administration (NMPA) approved bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy®; 50mg/200mg/25mg), a once-daily single tablet regimen, for the treatment of HIV-1 infections, in patients without present or past evidence of viral resistance to the integrase inhibitor class, emtricitabine or tenofovir. The approval was based on the data from the four phase III studies, including s

tudies 1489 and 1490 in treatment-naïve HIV-1 infected adult patients, and Studies 1844 and 1878 in virologically suppressed adult patients [see trials below] [11] .

In March 2019, Japan’s Ministry of Health, Labour and Welfare (MHLW) approved the fixed-dose combination of bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy®; 50mg/200mg/25mg), once-daily single tablet regimen for the treatment of HIV-1 infections. The approval was supported by data from the four phase III trials - trials 1489 and 1490 in treatment-naïve HIV-1 infected adults, and studies 1844 and 1878 in virologically suppressed adults [see trials below] [12] .

In October 2018, the Hong Kong Department of Health approved fixed-dose combination of bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy®; 50mg/200mg/25mg), once-daily single tablet regimen, for the treatment of HIV-1 infection in adults. The approval was supported by positive data from studies 1489, 1490, 1844 and 1878 [see below] [13] .

In July 2018, the Therapeutic Goods Administration (TGA) approved the use of bictegravir/emtricitabine/tenofovir alafenamide tablet (Biktarvy®) in Australia, for the treatment of HIV-1 infection in adults who were antiretroviral therapy (ART)-naive or to replace the antiretroviral regimen in those who were virologically-suppressed (TGA website, August 2018). Earlier in March 2018, Gilead had submitted a regulatory application to the TGA for the use of bictegravir/emtricitabine/tenofovir alafenamide tablet in patients with HIV-1 infection in Australia [14] .

In March 2021, Pooled efficacy and adverse event results from phase III trials 1489 and 1490 [see below] were presented at the 28th Conference on Retroviruses and Opportunistic Infections (CROI-2021) [15] [16] .

In July 2020, Pooled efficacy and adverse event results from phase III trials of 1844, 1878, 4030 and 4449 [See below] were presented at the 23rd International AIDS Conference (AIDS-2020) [17] .

In March 2019, NEAT ID Foundation, Gilead Sciences and Janssen Pharmaceuticals initiated the LAPTOP phase III trial to compare the efficacy of bictegravir/emtricitabine/tenofovir alafenamide versus cobicistat/darunavir/emtricitabine/tenofovir alafenamide [see AdisInsight drug profile800035274] , in patients with advanced HIV-1 infections (NEAT44; NCT03696160). Evaluation of the time to treatment failure is the defined primary endpoint of the trial. The open label trial is presently enrolling approximately 440 patients in the UK and the enrolment may expand to other countries [18] .

In August 2020, Gilead Sciences completed the phase IIIb BRAAVE 2020 trial that evaluated the efficacy of switching from a regimen of two Nucleos(t)Ide Reverse Transcriptase Inhibitors (NRTI) plus a third agent to a fixed-dose combination of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (Biktarvy®; 50mg/200mg/25mg), in HIV-1 infected, virologically suppressed patients (GS-US-380-4580; NCT03631732). The randomised, open- label trial was initiated in August 2018, and enrolled 496 patients in the US. In March 2020, Gilead Sciences released data from the study. The company also presented data from the study at the 27th Conference on Retroviruses and Opportunistic Infections (CROI-2020) [19] [20] . In October 2020, Updated efficacy data from the trial were released by Gilead Sciences and also presented at the IDWeek 2020 (IDW-2020) [21] [22] .

In May 2018, Gilead Sciences initiated a a phase III trial to evaluate the safety and efficacy of bictegravir/emtricitabine/tenofovir alafenamide versus dolutegravir + emtricitabine/tenofovir disoproxil fumarate in treatment naive, HIV-1 and hepatitis B co-infected patients (EudraCT2018-000926-79; GS-US-380-4458, NCT03547908). The randomised, double blind trial is enrolling approximately 240 patients in the US and Puerto Rico [23] .

In May 2020, Gilead Sciences completed a phase III trial that evaluated the efficacy of switching from an elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fixed-dose combination regimen or a tenofovir disoproxil fumarate containing regimen to fixed-dose combination of bictegravir /emtricitabine/tenofovir alafenamide, in elderly virologically-suppressed, HIV-1 infected subjects (GS-US380-4449; EudraCT2017-003428-61; NCT03405935). The open label trial was initiated in March 2018, and enrolled 86 patients in Belgium, United Kingdom, Italy, France and Spain [24] .

In February 2021, Gilead completed a phase III trial that was designed to evaluate the safety and efficacy of switching from a regimen of either dolutegravir [see AdisInsight drug profile 800027913] and emtricitabine/tenofovir alafenamide [see AdisInsight drug profile 800040899] or dolutegravir and emtricitabine/tenofovir disoproxil fumarate [see AdisInsight drug profile 800019370] to a fixed dose combination of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), when compared with dolutegravir and emtricitabine/tenofovir disoproxil fumarate in HIV-1 infected patients who are virologically suppressed (GS-US-380-4030; EudraCT2017-000308-17; NCT03110380). The primary endpoint of the trial is the proportion of patients with virologic failure (HIV-1 RNA ≥ 50 copies/mL) at week 48. The double-blind, randomised, placebo-controlled trial initiated in June 2017, enrolled 567 patients in the US, Austria, Canada, France, Germany and Puerto Rico [25] . In July 2020, Gilead sciences presented the clinical data at the 23rd International AIDS Conference (AIDS-2020) [17] .

In May 2017, Gilead Sciences announced that four phase III studies (studies 1489, 1490, 1844 and 1878) [see below] of bictegravir/emtricitabine/tenofovir alafenamide 50mg/200mg/25mg for the treatment of HIV-1 infection met their primary objectives of non-inferiority. The combination of bictegravir/emtricitabine/tenofovir alafenamide demonstrated high Efficacy and zero Resistance through 48 weeks in clinical trials [26] .

Pooled efficacy and adverse event results from phase III trials 1489 and 1490 [see below] were presented at the 27th Conference on Retroviruses and Opportunistic Infections (CROI-2020) [27] [28] .

In July 2021, Gilead Sciences completed phase III trial which evaluated the efficacy of a fixed dose combination containing bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus a FDC containing abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) in HIV-1 infected, antiretroviral treatment naive-adults (GS-US-380-1489; 2015-004024-54; NCT02607930). The randomised, double-blind trial was initiated in November 2015 and enrolled 631 patients in the US, Belgium, Canada, Dominican Republic, France, Germany, Italy, Puerto Rico, Spain, and the UK. In October 2018, positive safety and efficacy results were announced from the trial [29] [30] [31] . In March 2021, the company presented pooled results of the two studies (study 1489 and study 1490) at the 28th Conference on Retroviruses and Opportunistic Infections (CROI-2021) [32] .

In November 2015, Gilead initiated a randomised 1:1, double-blind phase III trial to evaluate the safety and efficacy of bictegravir/emtricitabine/tenofovir alafenamide (50/200/25mg) tablets, in comparison with dolutegravir plus emtricitabine/tenofovir alafenamide, in 645 HIV-infected antiretroviral treatment-naive patients (GS-US-380-1490; 2015-003988-10; NCT02607956). The primary endpoint of the study is the proportion of participants who achieve HIV-1 RNA < 50 copies/mL, as defined by the US FDA snapshot algorithm, at week 48 of the treatment. The study remains blinded through 144 weeks. Recruitment is under progress in the US, Australia, Gabon, Dominican Republic, France, Germany, Canada, Belgium, Italy, Puerto Rico, Spain and the UK. In July 2017, positive results were announced from the trial. In October 2018, updated data were released by the company [33] [30] [34] .

In March 2018, Gilead Sciences reported that, through Week 48, bictegravir/emtricitabine/tenofovir alafenamide (50/200/25mg) was statistically non-inferior to abacavir, dolutegravir and lamivudine (600/50/300mg) (ABC/DTG/3TC) with a numerically lower incidence of mild or moderate study drug-related adverse events and no treatment-emergent resistance (GS-US-380-1844; 2015-004025-14; NCT02603120) [35] . The third randomised 1:1, double-blind phase III trial was initiated in November 2015, to evaluate the safety and efficacy of switching from a regimen of dolutegravir plus abacavir/lamivudine or a fixed-dose combination of abacavir/dolutegravir/lamivudine to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), in comparison with continuing with the former treatments, in approximately 520 virologically suppressed HIV-1 infected patients. The primary endpoint is the proportion of participants who achieve HIV-1 RNA < 50 copies/mL, as defined by the US FDA snapshot algorithm, at week 48 of the treatment, and the lower bound of the 95% CI for non-inferiority is 4%. The patients continuing in the study enter an open-label extension receiving BIC/FTC/TAF after week 48. The trial is expected to enrol 567 patients in the US, Australia, France, Germany, Canada, Belgium, Italy, Puerto Rico, Spain and the UK [36] . In July 2019, company released results from the study [37] . In October 2020, updated results from the trial were presented at IDWeek 2020 (IDW-2020) [38] .

In December 2019, Gilead Sciences completed a phase III trial that evaluated the safety and efficacy of switching to a fixed dose combination of bictegravir/emtricitabine/tenofovir alafenamide 50/200/25mg (BIC/FTC/TAF) tablet versus continuing on a regimen consisting of boosted atazanavir 300mg capsule or darunavir 800mg tablet plus either emtricitabine/tenofovir disoproxil fumarate (FTC/TDF, 200/300mg) tablet or abacavir/lamivudine (ABC/3TC, 600/300mg) tablet [see AdisInsight drug profile 800016533] in patients with HIV-1 infection, who are virologically suppressed (GS-US380-1878; EudraCT2015-004011-20; NCT02603107). The randomised, open label trial was initiated in November 2015, and enrolled 578 patients in the US, Australia, Belgium, Canada, Dominican Republic, France, Germany, Italy, Puerto Rico, Spain and the UK. In October 2017, data demonstrating that BIC/FTC/TAF was found to be statistically non-inferior to regimens containing boosted protease inhibitor (bPI) and demonstrated no treatment-emergent resistance at 48 weeks were presented at the IDWeek 2017 [39] [40] .

Gilead Sciences, in January 2019, completed a phase III study that evaluated the safety and efficacy of switching to bictegravir/emtricitabine/tenofovir alafenamide (50/200/25mg) tablet versus continuing on a regimen consisting of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (150/150/200/10 mg) tablet, elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF), or atazanavir 300mg capsule plus ritonavir 100mg tablet plus emtricitabine/tenofovir disoproxil fumarate (200/300 mg) tablet in virologically suppressed HIV-1 infected women (Study 1961; GS-US-380-1961; NCT02652624). The primary end point of the trial is to determine the percentage of participants with HIV-1 RNA ≥ 50 copies/mL at week 48 as determined by the US FDA defined snapshot algorithm. The trial was designed to recruit patients who completed the 48-week open-label extension (OLE) visit or any post week 48 OLE visits in Gilead-sponsored study GS‑US‑236‑0128, or completed the 96-week visit or any post week 96 visits in Gilead-sponsored study GS‑US-292-0109. The open-label randomised, trial was initiated in February 2016 and enroled 472 patients in the US, Puerto Rico, Russia, Thailand, Uganda and Dominican Republic [41] . In March 2018, the company presented 48-week results of the study [42] . In July 2019, company released results from the study [37] .

In September 2016, Gilead Sciences initiated a phase II/III trial to evaluate the steady state pharmacokinetics (PK) for bictegravir and confirm the dose of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) fixed-dose combination (FDC) in HIV-1 infected, virologically suppressed adolescents (12 to < 18 years of age) and children (6 to < 12 years of age) (EudraCT2016-002345-39; P316/2015; NCT02881320; GS-US-380-1474). The trial is enrolling approximately 125 patients in the US, Uganda, Thailand and South Africa [43] . In March 2018, the company presented safety, efficacy and pharmacokinetics data of bictegravir/emtricitabine/tenofovir alafenamide at the 25th Conference on Retroviruses and Opportunistic Infections (CROI-2018) [44] . In March 2019, the company presented updated 48 week data at the 26th Conference on Retroviruses and Opportunistic Infections (CROI-2019). Data demonstrated that bictegravir/emtricitabine/tenofovir alafenamide maintained high rates of virologic suppression with a low incidence of study drug-related adverse events and no treatment-emergent resistance at week 48. Results evaluating the effect of bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy) tablet on adherence showed that all patients reported that the size and shape of the Biktarvy tablet was acceptable and the taste was palatable and 99% of the patient population receiving the drug adhered to the regime [45] [46] . In March 2020, pharmacokinetics, efficacy and safety data from the trial was presented at the 27th Conference on Retroviruses and Opportunistic Infections (CROI-2020) [47] .

As at March 2021, Gilead Sciences completed a phase I trial that evaluated the effect of once-weekly (QW) rifapentine administration on pharmacokinetics (PK) of B/F/TAF to assess their ability to be co-administered in patients with HIV and latent TB co-infection. The open label trial enrolled patients in the US [48] . In March 2021, pharmacokinetic data from the trial was presented at 28th Conference on Retroviruses and Opportunistic Infections (CROI-2021) [49] .

Before March 2020, Gilead Sciences completed a phase I trial which assessed the relative bioavailability (rBA) and food-effect of the low dose tablet in healthy adult participants. The pharmacokinetics was then confirmed in children with HIV. The randomised, crossover trial enrolled 54 participants. In March 2020, pharmacokinetics and safety data from the trial was presented at the 27th Conference on Retroviruses and Opportunistic Infections (CROI-2020) [50] [51] .

In June 2019, Gilead Sciences initiated a phase I trial to evaluate the pharmacokinetic, safety and efficacy of B/F/TAF in HIV-1 infected, virologically suppressed, pregnant women in their second and third trimesters (NCT03960645; GS-US380-5310). The open-label trial is enrolling approximately 35 patients in the US [52] .

Gilead Sciences completed a blinded, placebo-controlled, crossover, phase I trial that assess the safety, efficacy, pharmacokinetics and pharmacodynamics of metformin following co-administration with bictegravir/emtricitabine/tenofovir alafenamide in 32 healthy volunteers. The volunteers were randomised 1:1 to receive either combination drug or placebo once daily for nine days followed by a three-day washout. Following four-days of combination drug or placebo, volunteers received 850 mg metformin at 12 hours post-dose of combination drug or placebo, and 500 mg twice daily for additional four days [53] . In October 2017, the company presented results of the trial at the IDWeek 2017 (IDW-2017) [54] .

In October 2020, Gilead Sciences presented pharmacodynamics data from in vitro study in HIV-1 infections at IDWeek 2020 (IDW-2020) [55] .

Results evaluating effect of bictegravir/emtricitabine/tenofovir alafenamide in post-exposure prophylaxis (PEP)/event-driven post-exposure prophylaxis (PrEP) in rhesus macaques were presented at the 27th Conference on Retroviruses and Opportunistic Infections (CROI-2020) [56] .

Labelling information

The US FDA in June 2019, approved labeling revisions to bictegravir/emtricitabine/tenofovir alafenamide to expand the patient population so as to include HIV-1 infected paediatric patients weighing at least 25kg [57] .

The US FDA approved label carries a black box warning related to occurrence of severe acute exacerbation of hepatitis B, in patients co-infected with HIV-1 and HBV infections, following discontinuation of products containing emtricitabine and/or tenofovir disoproxil fumarate, and similar symptoms can occur, following discontinuation of bictegravir/emtricitabine/tenofovir alafenamide [5] .

Patent Information

As at December 2020, Gilead Sciences was issued patent protection for bictegravir/emtricitabine/tenofovir alafenamide in the US and in the European Union valid through 2033 [58] .

Patent disputes

In February 2018, ViiV Healthcare announced that it filed patent infringement litigation against Gilead Sciences over bictegravir in the US District Court for the District of Delaware (US Patent No. 8 129 385) and the Canadian Federal Court in Toronto (Canadian Patent No. 2 606 282). ViiV Healthcare will seek to prove that Gilead Sciences' triple combination HIV drug containing the bictegravir infringes the former's patent covering dolutegravir [see Adis Insight Drug profile 800027913] and many other compounds that include dolutegravir’s unique chemical scaffold [59] .

The U.S. District Court, in July 2016, dismissed AIDS Healthcare Foundation's lawsuit, filed against Gilead Sciences in January 2016, alleging drug patent manipulation and anti-trust claims regarding slightly different formulations of tenofovir, specifically tenofovir alafenamide used in Gilead's multiple fixed dose combination drugs, including bictegravir/emtricitabine/tenofovir alafenamide. AIDS Healthcare Foundation plans to appeal against the dismissal [60] .

Drug Properties & Chemical Synopsis

  • Route of administration PO
  • Formulation Tablet
  • Class Antiretrovirals, Deoxyribonucleosides, Oxazepines, Purines, Pyrazines, Pyridones, Pyrimidine nucleosides, Small molecules
  • Target DNA polymerase beta; DNA polymerase gamma; DNA polymerase I; DNA polymerase II; HIV integrase; HIV reverse transcriptase
  • Mechanism of Action DNA polymerase beta inhibitors; DNA polymerase gamma inhibitors; DNA polymerase I inhibitors; DNA polymerase II inhibitors; HIV integrase inhibitors; HIV reverse transcriptase inhibitors
  • WHO ATC code

    J05A-R20 (Emtricitabine, tenofovir alafenamide and bictegravir)

  • EPhMRA code

    J5C (HIV antivirals)

    J5C1 (Nucleoside and nucleotide reverse transcriptase inhibitors)

  • Chemical name 2,5-Methanopyrido(1',2':4,5)pyrazino(2,1-b)(1,3)oxazepine-10-carboxamide, 2,3,4,5,7,9,13,13a-octahydro-8-hydroxy-7,9-dioxo-N-((2,4,6-trifluorophenyl)methyl)-, (2R,5S,13aR)- / 2(1H)-Pyrimidinone, 4-amino-5-fluoro-1-(2-(hydroxymethyl)-1,3-oxathiolan-5-yl)-, (2R-cis)- / L-Alanine, N-((S)-(((1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy)methyl)phenoxyphosphinyl)-, 1-methylethyl ester
  • Molecular formula C21 H18 F3 N3 O5 . C8-H10-F-N3-O3-S . C21 H29 N6 O5 P
  • SMILES O1C2N(C3CCC1C3)C(C1N(C2)C=C(C(C=1O)=O)C(=O)NCC1C(=CC(=CC=1F)F)F)=O.C1(N=C(C(=CN1C1CSC(O1)CO)F)N)=O.C(C(NP(=O)(OC1C=CC=CC=1)COC(CN1C=NC2=C(N=CN=C12)N)C)C)(=O)OC(C)C
  • Chemical Structure

Biomarkers Sourced From Trials

Indication Biomarker Function Biomarker Name Number of Trials

coronary artery disease

Outcome Measure

Monocyte differentiation antigen CD14

Interleukin-6 (IL-6)

CD163

Cardiac Troponin I

C-reactive protein (CRP)

BNP

1

1

1

1

1

1

hepatitis B

Outcome Measure

T-cell surface antigen CD4

1

HIV infections

Detailed Description

T-cell surface antigen CD4

T-Cell differentiation antigen CD8

MIR155 host gene

4

1

1

HIV infections

Eligibility Criteria

T-cell surface antigen CD4

proteasome 26S subunit, non-ATPase 8

1

1

HIV infections

Outcome Measure

T-cell surface antigen CD4

T-Cell differentiation antigen CD8

Monocyte differentiation antigen CD14

MIR155 host gene

Interleukin-6 (IL-6)

Insulin

IGFBP7

CD163

Cardiac Troponin I

C-reactive protein (CRP)

BNP

3

3

1

1

1

1

1

1

1

2

1

HIV-1 infections

Outcome Measure

Thyroid stimulating hormone beta (TSH)

T-cell surface antigen CD4

T-Cell differentiation antigen CD8

RBP4

Prolactin

Pro-opiomelanocortin (POMC

MIR155 host gene

Leptin

Interleukin-6 (IL-6)

Insulin

IGFBP7

Hydrocortisone

HLA-B

Ghrelin

FSH

Creatinine

Beta-2-microglobulin (B2M)

B-cell lymphoma 2 (Bcl-2)

Adiponectin (ADIPOQ)

1

22

6

1

1

1

1

1

1

1

1

1

1

1

1

2

1

1

1

HIV-1 infections

Brief Title

SERPINA13P

immunoglobulin superfamily member 9

1

1

HIV-1 infections

Detailed Description

T-cell surface antigen CD4

matrilin 1, cartilage matrix protein

Cytidine monophosphate

2

1

1

HIV-1 infections

Eligibility Criteria

Thymidine

T-cell surface antigen CD4

PITRM1

matrilin 1, cartilage matrix protein

Interferon Gamma (IFNg)

immunoglobulin superfamily member 9

Epidermal growth factor receptor (EGFR)

Cytidine monophosphate

Alpha-fetoprotein (AFP)

1

5

3

1

1

1

1

1

1

HIV-1 infections

Official Title

SERPINA13P

immunoglobulin superfamily member 9

2

1

HIV-1 infections

Brief Summary

T-cell surface antigen CD4

T-Cell differentiation antigen CD8

MIR155 host gene

IGFBP7

2

1

1

1

Biomarker

Drug Name Biomarker Name Biomarker Function
Bictegravir/emtricitabine/tenofovir alafenamide - Gilead Sciences adhesion regulating molecule 1 Arm Group Label
Adiponectin (ADIPOQ) Detailed Description, Outcome Measure
ADP-ribosyltransferase 4 (Dombrock blood group) Eligibility Criteria
Alpha-fetoprotein (AFP) Eligibility Criteria
B-cell lymphoma 2 (Bcl-2) Outcome Measure
BCL2 interacting killer Outcome Measure
Beta-2-microglobulin (B2M) Outcome Measure
BNP Outcome Measure
C-reactive protein (CRP) Outcome Measure
Cardiac Troponin I Outcome Measure
CD163 Outcome Measure
Creatinine Outcome Measure
Cytidine monophosphate Detailed Description, Eligibility Criteria
Epidermal growth factor receptor (EGFR) Eligibility Criteria
Estradiol-17beta 3-sulfate Eligibility Criteria
FSH Eligibility Criteria, Outcome Measure
Ghrelin Outcome Measure
hematological and neurological expressed 1 Arm Group Label
HLA-B Outcome Measure
Hydrocortisone Outcome Measure
IGFBP7 Brief Summary, Outcome Measure
immunoglobulin superfamily member 9 Brief Title, Eligibility Criteria, Official Title
Insulin Outcome Measure
Interferon Gamma (IFNg) Eligibility Criteria
Interleukin-10 (IL-10) Detailed Description
Interleukin-18 (IL-18) Detailed Description
Interleukin-6 (IL-6) Detailed Description, Outcome Measure
Interleukin-8 (IL-8) Detailed Description
Leptin Detailed Description, Outcome Measure
matrilin 1, cartilage matrix protein Detailed Description, Eligibility Criteria
MIR155 host gene Brief Summary, Detailed Description, Outcome Measure
Monocyte chemoattractant protein-1 (MCP-1/CCL2) Detailed Description
Monocyte differentiation antigen CD14 Outcome Measure
NOB1 Eligibility Criteria
PHD finger protein 5A Outcome Measure
PITRM1 Eligibility Criteria
Pro-opiomelanocortin (POMC Outcome Measure
Prolactin Outcome Measure
proteasome 26S subunit, non-ATPase 8 Eligibility Criteria
RBP4 Outcome Measure
SERPINA13P Brief Title, Eligibility Criteria, Official Title
SRY Outcome Measure
T-Cell differentiation antigen CD8 Brief Summary, Detailed Description, Outcome Measure
T-cell surface antigen CD4 Brief Summary, Detailed Description, Eligibility Criteria, Outcome Measure
Thymidine Eligibility Criteria
Thyroid stimulating hormone beta (TSH) Outcome Measure
Tumor necrosis factor alpha (TNF-alpha) Detailed Description
For more detail, check out BiomarkerBase: the leading source of information about biomarkers used in drug development and diagnostic tests, tracking a comprehensive list of biomarker uses worldwide by over 800 companies

Development Status

Summary Table

Indication Qualifier Patient Segment Phase Countries Route / Formulation Developers Event Date
HIV-1 infections - Treatment-experienced Marketed Canada, Denmark, Netherlands, Norway, Poland, USA, United Kingdom PO / Tablet Gilead Sciences 16 Aug 2019
HIV-1 infections - In adolescents, In children Marketed USA PO / Tablet Gilead Sciences 18 Oct 2021
HIV-1 infections - Treatment-naive Marketed Canada, Denmark, Netherlands, Norway, Poland, USA, United Kingdom PO / Tablet Gilead Sciences 16 Aug 2019
HIV-1 infections - Treatment-naive Registered Australia, China, European Union, Hong Kong, Iceland, Japan, Liechtenstein, Puerto Rico PO / Tablet Gilead Sciences 09 Aug 2019
HIV-1 infections - Treatment-experienced Registered Australia, China, European Union, Hong Kong, Iceland, Japan, Liechtenstein, Puerto Rico PO / Tablet Gilead Sciences 09 Aug 2019
HIV-1 infections - Treatment-experienced Phase III Dominican Republic, Russia, Thailand, Uganda PO / Tablet Gilead Sciences 01 Feb 2016
HIV-1 infections - In the elderly Phase III Belgium, France, Italy, Spain, United Kingdom PO / Tablet Gilead Sciences 01 Mar 2018
HIV-1 infections - Treatment-naive Phase III Dominican Republic, Gabon PO / Tablet Gilead Sciences 13 Nov 2015
HIV-1 infections - In adolescents, In children Phase II/III South Africa, Thailand, Uganda PO / Tablet Gilead Sciences 01 Sep 2016
HIV-1 infections - Prevention Preclinical USA PO / Tablet Gilead Sciences 08 Mar 2020

Commercial Information

Involved Organisations

Organisation Involvement Countries
Gilead Sciences Originator USA
Gilead Sciences Owner USA
NEAT ID Foundation Collaborator United-Kingdom
Janssen Pharmaceuticals Collaborator USA

Brand Names

Brand Name Organisations Indications Countries
Biktarvy Gilead Sciences HIV-1 infections USA

Credit Suisse Market Status

Indication Region Company Phase Expected Launch Year Probability of Success% Patent Expiry Year Expected Generic Entry Last Update
HIV with TAF ex US Gilead Sciences Marketed 2018 100 2033 01 Dec 2033 01 Feb 2021
HIV with TAF US Gilead Sciences Marketed 2018 100 2033 01 Dec 2033 01 Feb 2021

Credit Suisse Financial Forecast

Indication Region 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 Last Update
HIV with TAF ex US 0 0 40 513 1130 1399 1630 1800 1940 2000 01 Feb 2021
HIV with TAF US 0 0 1144 4225 6005 6650 7310 7785 8060 8347 01 Feb 2021
Total 0 0 1184 4738 7135 8049 8940 9585 10000 10347

Scientific Summary

  • Adverse Events Occasional: Headache; Nasopharyngitis; Respiratory tract infections; Urinary tract infections; Vulvovaginal candidiasis

Pharmacokinetics

In a phase II/III trial, treatment with bictegravir/emtricitabine/tenofovir alafenamide demonstrated therapeutic plasma concentrations of all components of bictegravir/emtricitabine/tenofovir. Geometric least squares mean ratios and 90% CIs for BIC AUCtau and Cmax in children versus adults were within 50-200%; BIC Ctau was 32% lower and exposures were within the range of historical data [47] [44] [43] .

Results of the crossover phase I study in 32 healthy volunteers demonstrated that inhibition of renal transporters OCT2/MATE1 by bictegravir led to a slight increase of metformin plasma exposure upon co-administration with bictegravir/emtricitabine/tenofovir alafenamide. Metformin plasma AUCtau was increased 39% (%GMR [90% CI]: 139 [131, 148]) with bictegravir/emtricitabine/tenofovir alafenamide versus placebo, with no change in median plasma t1/2 (combination drugs: 6.4 hours; placebo: 7.1 hours). Metformin renal clearance decreased 31% with bictegravir/emtricitabine/tenofovir alafenamide versus placebo [54] [53] .

Treatment with Bictegravir /emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in a phase I trial for HIV infections showed that compared to fasted, high-fat meal did not alter BIC or FTC PK; TAF AUCinf increased 42%, Cmax decreased 44%. 15% (adult tab fasted, or LDT fed) and geometric least-squares mean (GLSM) ratios and 90% CIs for BIC AUCtau and Cmax in children vs adults were within 50-200%. Mean BIC Ctau was 32% lower (Table). Exposures of FTC (mean AUCtau=14,900 h*ng/mL), TAF (mean AUCtau=305 h*ng/mL) and TFV (mean AUCtau=339 h*ng/mL) were within the range of historical data [50] [51] .

Results from the phase III trial in patients who switched to Bictegravir/Emtracitabine/Tenofovir from Dolutegravir/Abacavir/Lamivudine demonstrated stable GFR and lipid levels with slight increase in LDL at 96 weeks [38] [36] .

Results from phase I trial in HIV negative volunteers receiving Bictegravir (BIC)/emtricitabine/tenofovir alafenamide (B/F/TAF) demonstrated significant decline in BIC C tau concentration following administration of B/F/TAF with rifapentine (RPT). Once a week administration of RPT decreased BIC C tau by ~40% on day 22 (co-dose) and by ~57% on day 30 (12-hr stagger). BIC C tau decline at the nadir was ~83%, occurring 3-4 days post RPT dosing. Notably BIC C tau did not rebound back to steady state concentrations between RPT doses. 12-hour staggered administration of RPT resulted in a more pronounced decline in BIC C tau compared to its co-administration. No clinically relevant changes in the pharmacokinetics of emtricitabine, tenofovir and tenofovir metabolite were observed upon administration with RPT [49] [48] .

Adverse Events

In a phase III trial (Study 1489), in patients with HIV-1 infections, the fixed dose combination of bictegravir/emtricitabine/tenofovir alafenamide was well tolerated through week 96. The most commonly reported adverse events with bictegravir/emtricitabine/tenofovir alafenamide and abacavir/dolutegravir/lamivudine were nausea (11% vs. 24%), diarrhoea (15% vs. 16%) and headache (13% vs. 16%), respectively. Discontinuations due to adverse events were low in both groups with only 2% (n = 5) reported in abacavir/dolutegravir/lamivudine arm and none in the bictegravir/emtricitabine/tenofovir alafenamide arm. None of the patients randomised to either arm developed treatment-emergent resistance. There were no renal discontinuations and no cases of proximal renal tubulopathy or fanconi syndrome in the bictegravir/emtricitabine/tenofovir alafenamide treatment group. The trial randomised 629 treatment-naïve adults with HIV to receive bictegravir/emtricitabine/tenofovir alafenamide or abacavir/dolutegravir/lamivudine [29] [30] [31] .

In a phase III trial (Study 1490), bictegravir/emtricitabine/tenofovir alafenamide was well-tolerated with low discontinuations due to adverse events in both treatment arms (2% (n=6) versus 2% (n=5) [1 bictegravir/emtricitabine/tenofovir alafenamide and 4 dolutegravir plus emtricitabine/tenofovir alafenamide, after week 48]). The most commonly reported adverse events (all grades) were diarrhoea (18% versus 16%) and headache (16% versus 15%). There were fewer treatment-related adverse events (all grades) in the treatment arm, compared with dolutegravir plus emtricitabine/tenofovir alafenamide (20% versus 28%). Lipid changes were not significantly different between the two arms, and there were no renal discontinuations or cases of proximal renal tubulopathy. Earlier, it was reported that the most commonly reported adverse events with bictegravir/emtricitabine/tenofovir alafenamide and dolutegravir plus emtricitabine/tenofovir alafenamide were headache (13% versus 12%) and diarrhoea (12% versus 12%), respectively. There were no renal discontinuations or cases of proximal renal tubulopathy. Discontinuations due to adverse events were low in both treatment arms. The trial randomised 645 treatment-naïve adults with HIV to receive bictegravir/emtricitabine/tenofovir alafenamide or dolutegravir plus emtricitabine/tenofovir alafenamide [33] [30] [34] .

In four phase III studies (Studies 1489, 1490, 1844 and 1878), bictegravir/emtricitabine/tenofovir alafenamide 50mg/200mg/25mg was well tolerated. Treatment-emergent virological resistance was not seen. No patients discontinued study medication due to renal events and no cases of proximal renal tubulopathy or Fanconi syndrome were observed. Diarrhoea, nausea and headache were the most common adverse reactions [26] [31] [34] [36] [40] .

In the phase III Study 1878, most commonly reported adverse events (all grades) in both, study and comparator arms included headache, diarrhoea, nasopharyngitis and upper respiratory tract infection. No renal adverse events leading to discontinuations or cases of proximal renal tubulopathy occurred with bictegravir, emtricitabine and tenofovir alafenamide BIC/FTC/TAF. The incidence of grade 3 or 4 adverse events was 4% (n = 13) for the BIC/FTC/TAF arm versus 6% (n = 18) for the bPI arm; the incidence of grade 3 or 4 laboratory abnormalities was 16% (n = 45) for the BIC/FTC/TAF arm versus 29% (n = 83) for the bPI arm. The study was conducted in 577 virologically suppressed adults with HIV taking regimens of boosted atazanavir (ATV) or darunavir (DRV) + abacavir/lamivudine (ABC/3TC) or FTC/tenofovir disoproxil fumarate (TDF) were randomized 1:1 to continue their bPI regimen or to switch to open-label co-formulated BIC/FTC/TAF once daily. BIC/FTC/TAF was generally well-tolerated with minimal changes to estimated glomerular filtration rate (eGFR), lipids and weight through 96 weeks. The most common drug-related adverse event was headache (2%) [39] [40] .

In a phase III trial at week 96, bictegravir/emtricitabine/tenofovir alafenamide was well-tolerated with low frequencies of serious adverse events [37] .The 48-week results of phase III trial (Study 1961) in 470 virologically suppressed HIV-1 infected women demonstrated no treatment-emergent resistance after switching to bictegravir/emtricitabine/tenofovir alafenamide (50/200/25mg) tablet at 48 weeks. Treatment-emergent resistance was not developed in any patients in the bictegravir/emtricitabine/tenofovir alafenamide treatment arm, while one patient taking cobicistat/elvitegravir/emtricitabine/tenofovir-alafenamide (Genvoya) in the baseline regimen (SBR) arm developed an emergent M184M/I/V mutation. No patient in either treatment group discontinued the study due to an adverse event. No renal adverse events leading to discontinuations and no cases of proximal renal tubulopathy occurred in either arm. The most commonly reported adverse events (all grades) in both arms included nasopharyngitis, upper respiratory tract infection, headache, vulvovaginal candidiasis and urinary tract infection [42] [41] .

Updated results from phase III trial demonstrated adverse events in 7% of the patients in the bictegravir/emtricitabine/tenofovir alafenamide arm. Most of the adverse events were grade 1 with most common was headache adverse events dur to premature study drug discontinuation were occurred in 1% of patients. Only 1 patient reported headache in open label phase [38] . Earlier data from the trial showed a lower incidence of study drug-related adverse events (AEs) versus the ABC/DTG/3TC arm (8%vs 16%, p = 0.006; all grades), which were primarily mild or moderate in severity. The difference between groups was primarily driven by numerically more drug-related gastrointestinal (flatulence, nausea, diarrhoea) and neuropsychiatric (abnormal dreams and insomnia) AEs in the ABC/DTG/3TC arm. Headache (3% in both arms) was the most common study drug-related AE observed. AEs in few patients led to premature trial discontinuation (2% vs 1%). No patients in either treatment arm developed treatment-emergent resistance through Week 48. No renal AEs leading to discontinuations or cases of proximal renal tubulopathy were reported in either treatment arms. Lipid profiles were unchanged after switching to bictegravir/emtricitabine/tenofovir alafenamide from ABC/DTG/3TC and bone mineral density changes from baseline were the same between arms, at Week 48. The trial is designed to evaluate the efficacy and safety of switching from a regimen containing abacavir, dolutegravir and lamivudine (600/50/300mg) (ABC/DTG/3TC) to bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg tablet od in virologically suppressed adults with HIV [35] [36] .

In a phase II/III study, bictegravir/emtricitabine/tenofovir alafenamide was well tolerated in adolescents through 24 weeks. The most common treatment emergent adverse events (AE) reported were upper respiratory tract infection (21%, 5 of 24), no other AE was observed in >2 participants, over a median duration of 25.6 weeks. No participant discontinued the treatment due to AE. Updated 48 week data showed that only 2% of the patients reported grade 1 abdominal discomfort as the only study drug-related adverse event. One patients discontinued the treatment due to AE (grade 2 insomnia and anxiety) at week 16. Through a median duration of exposure to study drug of 20.1 (18.0, 27.1) weeks, most common adverse events (AE) were abdominal pain, diarrhea, and upper respiratory tract infection (n=2 participants each); all AEs were grade 1 or 2; no child discontinued for AE. Related-AEs included neutropenia, irritability, and social avoidant behavior (n=1 each) [47] . [45] [44] [43] [46] .

Pooled four year follow-up results of the two phase III trials (study 1489 and study 1490) in HIV-infected antiretroviral treatment-naive patients showed long-term safety profile of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF). Across both studies, only one participant experienced an adverse events (AE) that led to drug discontinuation during the open-label extension (OLE) analysis window. Grade 3 or 4 drug-related AEs were rare. There were no discontinuations due to renal AEs [32] . Updated results from two phase III trials (Study 1489 and Study 1490) in patients with HIV-1 infections showed that through 144 weeks of therapy bictegravir/emtricitabine/tenofovir alafenamide was well-tolerated. Discontinuations due to adverse events were low across all groups (1% (n=6/634) for Biktarvy versus 2% (n=5/315) for DTG/ABC/3TC and 2% (n=6/325) for DTG + F/TAF). The proportion of drug-related adverse events (all grades) was 26% in the Biktarvy arm (n=165/634) versus 42% (n=132/315) for DTG/ABC/3TC and 29% (n=94/325) for DTG + F/TAF). The incidence of drug related nausea was 4% for Biktarvy versus 18% for DTG/ABC/3TC and 5% for DTG + F/TAF (p<0.0001 for Biktarvy versus DTG/ABC/3TC). The most commonly reported treatment-emergent adverse events (all grades) were diarrhoea (19% for Biktarvy versus 18% for DTG/ABC/3TC and 16% for DTG + F/TAF), headache (16% for Biktarvy versus 18% for DTG/ABC/3TC and 18% for DTG + F/TAF) and nasopharyngitis (14% for Biktarvy versus 17% for DTG/ABC/3TC and 19% for DTG + F/TAF) [62] [31] [34] .

In the phase IIIb BRAAVE 2020 trial, bictegravir/emtricitabine/tenofovir alafenamide was well-tolerated and no treatment-emergent resistance was detected in patients (n = 495) with HIV infection. Study drug-related AEs occurred in 10% of patents while on B/F/TAF; most were grade 1. Headache, diarrhoea and insomnia were the most common adverse events (AEs) in the study. Most of the treatment realted AEs were of grade 1. Drug was discontinued by 1.8% of patients treated with bictegravir/emtricitabine/tenofovir alafenamide, due to AEs and in none of the patients remaining on their baseline regimen [21] [19] [20] .

Pooled analysis

Pooled analysis of phase III trials 1489 and 1490 showed that the most common adverse events (AEs) in adults of 50 years of age in patients receiving B/F/TAF, DTG/ABC/3TC, 325 DTG + F/TAF were nasopharyngitis (20%, 22%, 25%), diarrhea (19%, 22%, 8%), and upper respiratory tract infection (16%, 17%, 12%), respectively. The most common AEs in adults of <50 years of age were diarrhea (19%, 18%, 18%), headache (17%, 18%, 19%), and nausea (11%, 26%, 15%). Treatment-related AEs occurred in 24%, 37%, and 29% of participants the frequency was 26%, 43% and 29% in participants <50 years (p < 0.001 for B/F/TAF vs DTG/ABC/3TC). Most treatment related AEs were grade 1. 50 patients discontinued due to AEs, 2% on B/F/TAF, 5% on DTG/ABC/3TC and 7% on DTG + F/TAF compared to 1% in each treatment group for participants <50 years. Among 50 with AEs leading to discontinuation, 1 on B/F/TAF, 1 on DTG/ABC/3TC and 3 on DTG+F/TAF were treatment-related. 1274 were randomised and treated (634 Bictegravir/emtricitabine/tenofovir alafenamide [B/F/TAF], 315 Abacavir/Dolutegravir/Lamivudine [DTG/ABC/3TC], 325 Dolutegravir + Emtricitabine/Tenofovir Alafenamide[DTG + F/TAF]) [28] [31] [34] .

Treatment with Bictegravir (BIC)/emtricitabine (FTC)/tenofovir alafenamide in a phase I trial for HIV infections showed that there were no discontinuations due to adverse events (AEs).19% (LDT fasted) participants had an AE (all Grade 1). There were no discontinuations due to AEs. Also, 75% participants had an AE (all Grade 1/2) [50] [51] .

Results from 1844, 1878, 4030 and 4449 trials showed that biktarvy was generally well-tolerated; 11 patients experienced a grade 1 or 2 study drug-related adverse event (AE), four of which discontinued the study. No patient experienced a grade 3 or 4 drug-related AE or virologic failure. Most common AEs were nasopharyngitis and arthralgia (7 percent each) [17] [36] [40] [25] [24] .

Results from phase I trial in HIV negative volunteers receiving Bictegravir (BIC)/emtricitabine/tenofovir alafenamide (B/F/TAF) was well tolerated and no adverse events were reported [49] [48] .

Pharmacodynamics

Results of the crossover phase I study in 32 healthy volunteers demonstrated that pharmacodynamic characteristics of metformin were not significantly affected by bictegravir/emtricitabine/tenofovir alafenamide when compared with placebo. Following metformin administration, statistically significant reduction of plasma glucose, and increase of plasma active glucagon-like peptide 1 (GLP-1) and lactate levels from baseline were observed (p < 0.001). Pharmacodynamic responses were not statistically different when metformin was administered with bictegravir/emtricitabine/tenofovir alafenamide when compared with placebo (p >0.05) [54] [53] .

Studies were conducted in rhesus macaques model of SHIV exposure, to evaluate event-driven post-exposure prophylaxis (PrEP)/post-exposure prophylaxis (PEP) regimens with emtricitabine(FTC)/tenofovir alafenamide(TAF) combined with different doses of bictegravir(BIC). After 8 virus challenges, BIC/FTC/TAF (25/200/25mg) protected all six animals in the -2h/+24h group, one of the six animals in the +24/+48h group and none in the +48/+72h group. FTC/TAF combination protected five of six animals in the -2h/+24h group, one in the +24/+48h group and none in the +48/+72h group. After 6 virus challenges, BIC/FTC/TAF (100/200/25mg) protected five of six animals in the +6h/+30h group, all six animals in the +12/+36h, four of six animals in the +24h/+48h, and three of six animals in the +48h/+72h group. FTC/TAF (200/25mg) combination protected three of six animals in the +6h/+30h group and four in the +12/+36h group [56] .

In in vitro studies, replicating alternating high and low drug exposures of bictegravir/emtricitabine/tenofovir alafenamide simulating variable adherence levels, showed high in vitro forgiveness and consistent protection against emergence of drug resistance to infections during simulations of short lapses in adherence. In wild-type HIV-1 (IIIb)-infected MT-2 cells, constant drug concentrations corresponding to full adherence (Cmin) did not lead to viral breakthrough (VB). In the study, using Cmin concentrations for one week followed by constant Cmin-2 exposures for 4 weeks, but there was no VB for bictegravir/emtricitabine/tenofovir alafenamide whereas dolutegravir and lamivudine (DTG+3TC) had VB and emergence of M184V/I in reverse transcriptase (RT). Using alternating drug exposures of Cmin (weeks 1 and 3) and Cmin-2 or Cmin-4 (weeks 2, 4, and 5), VB was not observed with bictegravir/emtricitabine/tenofovir alafenamide, and VB was decreased or delayed with dolutegravir and lamivudine compared with dolutegravir and lamivudine held at Cmin-2 or Cmin-4. The outcome of the study showed that higher dolutegravir and lamivudine exposure, whether constant or intermittent, was better at preventing or delaying VB than lower dolutegravir and lamivudine exposures, however dolutegravir and lamivudine was less forgiving than bictegravir/emtricitabine/tenofovir alafenamide [55] .

Therapeutic Trials

Updated results from a phase III trial (Study 1489) in patients with HIV-1 infections showed that through 96 weeks of therapy bictegravir/emtricitabine/tenofovir alafenamide was statistically non-inferior to a regimen of abacavir/dolutegravir/lamivudine and non-inferiority was maintained from the primary endpoint measurement at week 48. At week 96, 87.9% (n = 276/314) of patients taking bictegravir/emtricitabine/tenofovir alafenamide (50/200/25mg) tablets and 89.8 % (n = 283/315) of patients taking abacavir/dolutegravir/lamivudine (600/50/300mg) achieved the primary endpoint of HIV-1 RNA levels less than 50 copies/mL (difference: -1.9%, 95 percent CI: -6.3 percent to 3.1%, p = 0.78). Significantly less median change in estimated glomerular filtration rate (eGFR) from baseline to week 96 was observed with bictegravir/emtricitabine/tenofovir alafenamide (-7.8 mL/min) compared with abacavir/dolutegravir/lamivudine (-9.6 mL/min) (p = 0.01). In both the treatment groups in changes from median changes in proteinuria were similar. Lipid changes were not significantly different between the two arms. Similar mean percent changes from baseline in spine and hip bone mineral density were observed in the bictegravir/emtricitabine/tenofovir alafenamide group and abacavir/dolutegravir/lamivudine group (spine: -0.71 vs. -0.22, p = 0.14; hip: -1.13 vs. -1.26, p = 0.59). The trial randomised 629 treatment-naïve adults with HIV to receive bictegravir/emtricitabine/tenofovir alafenamide or abacavir/dolutegravir/lamivudine [29] [30] [31] .

Results from a phase III trial (Study 1490) demonstrated high efficacy and high barrier to resistance of bictegravir/emtricitabine/tenofovir alafenamide through 96 weeks. At week 96, non-inferiority was maintained from the primary endpoint measurement at week 48, with 84.1% (n=269/320) of patients taking bictegravir/emtricitabine/tenofovir alafenamide and 86.5% (n=281/325) of patients taking dolutegravir plus emtricitabine/tenofovir alafenamide achieving HIV-1 RNA levels less than 50 copies/mL (difference: -2.3%, 95% CI: -7.9% to 3.2%, p=0.41). Earlier, in the trial, it was reported that at week 48, 89% (286/320) of patients taking bictegravir/emtricitabine/tenofovir alafenamide (50/200/25mg) tablets and 92% (n=302/325) of patients taking dolutegravir plus emtricitabine/tenofovir alafenamide achieved the primary endpoint of HIV-1 RNA levels less than 50 copies/mL (difference: -3.5%, 95% CI: -7.9% to 1.0%, p=0.12). No patients in either treatment arm developed treatment-emergent resistance to any of the study drugs. Lipid changes were not significantly different between the two arms. The trial randomised 645 treatment-naïve adults with HIV to receive bictegravir/emtricitabine/tenofovir alafenamide or dolutegravir plus emtricitabine/tenofovir alafenamide [33] [30] [34] .

Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) 50mg/200mg/25mg met the primary endpoint of non-inferiority in all four phase III studies, with comparable proportions of patients having HIV-1 RNA < 50 copies/mL (Studies 1489 and 1490) and HIV-1 RNA ≥ 50 copies/mL (Studies 1844 and 1878). One patient randomised to the protease inhibitor arm in Study 1878 developed an abacavir resistance mutation (L74V). No patients randomised to the bictegravir or dolutegravir arms developed treatment-emergent resistance [26] [31] [34] [36] [40] .

In the phase III Study 1878, bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) was statistically non-inferior to regimens containing boosted protease inhibitor (bPI) with with 2% of patients in each group having HIV-1 RNA =50 c/mL (difference: 0.0%, 95% CI: -2.5% to 2.5%, p = 1.00); the proportion of patients with HIV-1 RNA <50 c/mL was 92% in the BIC/FTC/TAF arm and 89% in the bPI arm. No treatment emergent resistance was reported in the study arm. The study was conducted in 577 virologically suppressed adults with HIV taking regimens of boosted atazanavir (ATV) or darunavir (DRV) + abacavir/lamivudine (ABC/3TC) or FTC/tenofovir disoproxil fumarate (TDF) were randomized 1:1 to continue their bPI regimen or to switch to open-label coformulated BIC/FTC/TAF once daily [39] [40] .

In a phase III trial, at Week 96, 99.5% of women who received bictegravir/emtricitabine/tenofovir alafenamide throughout the study duration and 98.5% of women who switched to bictegravir/emtricitabine/tenofovir alafenamide at week 48 maintained virologic suppression, with no development of treatment-emergent resistance.The 48-week results of phase III trial (Study 1961) in 470 virologically suppressed HIV-1 infected women demonstrated that the primary endpoint of the study, switching to bictegravir/emtricitabine/tenofovir alafenamide (50/200/25mg) tablet was statistically non-inferior to regimens containing a boosted protease inhibitor (bPI) or boosted elvitegravir (baseline regimen, SBR) at 48 weeks, with 1.7% of participants in both the bictegravir/emtricitabine/tenofovir alafenamide and the SBR arms having HIV-1 RNA ≥50 c/mL (difference 0.0%; 95% CI: -2.9% to 2.9%, p = 1.00). The proportion of patients with HIV-1 RNA <50 c/mL was 95.7% in the bictegravir/emtricitabine/tenofovir alafenamide arm and 95.3% in the SBR arm, according to FDA snapshot algorithm [37] [42] [41] .

Updated results from phase III trial who switched to bictegravir/emtricitabine/tenofovir from Dolutegravir/Abacavir/Lamivudine demonstrated RNA < 50 c/mL maintained in 99-100% at all timepoints through maximum of 168 weeks. No participant develop resistance to the regimen [38] . Earlier data showed that at the primary endpoint of Week 48, switching to bictegravir/emtricitabine/tenofovir alafenamide was non-inferior to continuing ABC/DTG/3TC with 1.1% in the bictegravir/emtricitabine/tenofovir alafenamide arm and 0.4% in the ABC/DTG/3TC arm having HIV-1 RNA ≥50 c/mL (difference: 0.7%; 95% CI: -1.0% to 2.8%, p = 0.62). At week 48, no treatment-emergent resistance was detected, and no participants with pre-existing NRTI resistance mutations had HIV RNA >50 c/mL.The proportion of patients with HIV-1 RNA <50 c/mL was 93.6% and 95% in the bictegravir/emtricitabine/tenofovir alafenamide arm and ABC/DTG/3TC arm, respectively, according to FDA snapshot algorithm. The trial is designed to evaluate the efficacy and safety of switching from a regimen containing abacavir, dolutegravir and lamivudine (600/50/300mg) (ABC/DTG/3TC) to bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg tablet od in 565 virologically suppressed adults with HIV [37] [35] [36] .

In a phase II/III trial, updated 48 weeks data showed that an undetectable viral load, as defined by the US FDA snapshot algorithm was observed in 100% of the patients. The remaining one patient had a reported HIV-1 RNA level of 85 c/ml at week 48, but re-suppressed and achieved an undetectable viral load within two weeks. Treatment-emergent resistance was not reported in any patient. CD4 count remained stable, at week 48 [45] [43] [46] . Patients (n=24) treated with bictegravir/emtricitabine/tenofovir alafenamide failed to meet criteria for resistance testing, at week 24. Mean change in CD4 count from baseline was 44 cells/μL. No clinically relevant differences in drug exposures of B/F/TAF components were observed compared with data from adults [44] .The 12 week data showed mean (SD) adherence to study drug was high (97.1% [7.02]). Ten of 11 (91%) children had HIV-1 RNA <50 c/mL at W12. Mean increase in CD4 count from baseline was 42 cells/mL [47] .

In a long term, open-label follow-up of phase III GS-US-380-1844 and GS-US380-1878 trial for two year post 48 week primary endpoints in adults who switched to Biktarvy from abacavir, dolutegravir and lamivudine (600/50/300mg) (ABC/DTG/3TC) or a boosted protease inhibitor (PI)-based regimen, overall, 98% patients displayed higher virologic suppression (n=561/570) whereas 97% (155/159) population with preexisting drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs) also showed virologic suppression. Moreover 95% (42/44) subjects who were with archieved M184V/I also exhibited virologic suppression. Moreover, in a phase III GS-US-380-4030 in patients who switched from DTG+F/TAF or DTG+F/TDF to DTG+F/TAF or Biktarvy for 48 weeks, 99% (557/562) of all patients with any post-baseline visit and 99% (220/222) of patients with resistance to any class of anti-retroviral therapy, including those with archived M184V/I (79/81; 98 percent) had undetectable viral load (HIV-1 RNA <50 copies/mL) with no emergent drug resistance [17] [63] [36] [40] [25] .

Pooled four year follow-up results of the two phase III trials (study 1489 and study 1490) in HIV-infected antiretroviral treatment-naive patients showed that bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) was highly efficacious. Similar outcomes were demonstrated in participants who switched from dlutegravir/ abacavir/lamivudine (DTG/ABC/3TC)-containing regimens to B/F/TAF. The efficacy was >98% after week 48 at each study visit through week 192 in both studies. In participants initially randomised to B/F/TAF, the median change in weight from baseline to week 192 was 4.6 kg in study 1490 and 5.0 kg in study 1490. The mean percent changes (SD) in hip and spine bone mineral density (BMD) through week 192 were -1.5% (4.9) and -0.9% (5.2), respectively. At week 192, 13% of participants with baseline osteopenia in hip and 3% with osteopenia of the spine improved to normal, 4% with normal baseline hip and 6% with normal baseline spine BMD progressed to osteopenia and none developed osteoporosis [32] . Updated results from two phase III trial (study 1489 and study 1490) demonstrated that treatment with bictegravir/emtricitabine/ tenofovir (B/F/TAF) achieved high rates of viral suppression. Treatment outcomes by last on-treatment observation carried forward at week 144 for participants with and without transmitted drug resistance (TDR) was comparable (98% of those with primary TDR had HIV RNA <50 copies/mL vs. 97% of those without TDR). One participant had preexisting Q148H+G140S in IN and K70R and K103N in RT at baseline. This participant was randomized to B/F/TAF, had HIV-1 RNA <50 copies/mL at week 4 and maintained HIV-1 RNA <50 copies/mL through week 144. Out of 21 participants qualified for post-baseline resistance testing, 2/8 receiving B/F/TAF, 6/6 receiving dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) and 4/7 receiving dolutegravir + emtricitabine/tenofovir (DTG + F/TAF) participants had multiple confirmed virologic rebounds during the studies. No participant had emergent resistance to study drugs [16] [64] . Earlier results from the trials showed that through 144 weeks of therapy bictegravir/emtricitabine/tenofovir alafenamide was well-tolerated and demonstrated high rates of virologic suppression. At Week 144, non-inferiority was maintained from the primary endpoint measurement in both studies at Week 48, with a similar proportion of the Biktarvy group achieving virologic suppression (82 percent; n=518/634) as those taking DTG/ABC/3TC (84 percent; n=265/315) and DTG + F/TAF (84 percent; n=273/325). Across all treatment groups no participants developed treatment failure with treatment-emergent resistance. There were no discontinuations due to renal events and no cases of proximal renal tubulopathy or Fanconi syndrome in the Biktarvy treatment group. Similar reductions in median estimated glomerular filtration rate (eGFR) were observed across groups (-9.2 mL/min in patients taking Biktarvy vs. -11.7 mL/min in participants taking ABC/DTG/3TC versus -11.0 mL/min in participants taking DTG + F/TAF) at Week 144. Study 1489 also assessed other laboratory markers of renal and bone safety in patients taking Biktarvy and DTG/ABC/3TC. Participants in both treatment arms demonstrated similar median changes in proteinuria and mean percentage changes in hip and spine bone mineral density (BMD) from baseline. Small, statistically significant differences in the median change from baseline favoring DTG/ABC/3TC were observed for LDL, HDL and total cholesterol to HDL ratio [62] [31] [34] .

In a phase IIIb BRAAVE 2020 trial in patients (n = 495) with HIV infection, 1% (2/328) on bictegravir, emtricitabine, tenofovir alafenamide (B/F/TAF) vs 2% (3/165) on stay on their baseline regimen (SBR) had HIV-1 RNA ≥50 c/mL (difference -1.2%; 95% CI -4.8% to 0.9%) demonstrating noninferiority of B/F/TAF at week 24. 163 patients assigned to SBR completed week 24 and switched to B/F/TAF (SBR to B/F/TAF). At week 48, 1% (3/328) originally randomised to B/F/TAF and zero SBR to B/F/TAF had HIV-1 RNA ≥ 50 c/mL. The presence of baseline NRTI resistance did not affect the efficacy of B/F/TAF. The mean (SD) changes in CD4 were +7 cells/mm3 (189) for B/F/TAF and -8 cells/mm3 (159) for SBR to B/F/TAF. Median (IQR) weight increased 0.9 kg (-1.5, 4.1) and 0.6 kg (-1.0, 3.1) for B/F/TAF and SBR to B/F/TAF groups, respectively. In earlier reported results, antiviral efficacy was non-inferior in patients who switched to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) from a variety of regimens, including in patients with pre-existing NRTI resistance. Viral suppression was maintained till week 48, by 99% in the Biktarvy group (324/327) and 100% of study participants in the delayed switch group (162/162) maintained HIV-1 RNA <50 copies/mL [22] . Earlier results showed that viral suppression was maintained till week 24, by 96.3% of patients who switched to bictegravir/emtricitabine/tenofovir alafenamide and 94.5% of patients who stayed on their baseline regimen. Of the 328 patients who received B/F/TAF, 326 were supressed at their last visit through week 24 which included 100% (44/44) patient resistant to NRTI, 99% (68/69) resistant to NNRTI, 100% of patients resistant to protease inhibitor (PI) and integrase strand transferase inhibitor (INSTI) [21] [61] [19] [20] .

Pooled analysis:

Pooled analysis of phase III trials 1489 and 1490 demonstrates that in both studies >98% of participants who initiated treatment with therapy bictegravir/emtricitabine/tenofovir alafenamide and remained in the study achieved and maintained an undetectable viral load (HIV-1 RNA <50 copies/mL) at four years of follow-up (n=235/237 for study 1489, n=241/243 for study 1490). The high efficacy and durable viral suppression were also observed in participants who switched to therapy bictegravir/emtricitabine/tenofovir alafenamide from a dolutegravir-containing triple therapy for the 48-week OLE periods (n=212 for study 1489, n=225 for study 1490). No treatment-emergent resistance to any components of the therapy occurred in participants treated with therapy bictegravir/emtricitabine/tenofovir alafenamide. The data from a 144 week analysis demonstrated that people living with HIV who received initial therapy with combination reached and maintained an undetectable viral load with no treatment-emergent resistance through 144 weeks (n=634). In a subgroup analysis of participants with transmitted drug resistance (TDR, n=248) based on retrospective sequencing from the baseline, combination therapy achieved comparably high levels of durable viral suppression through 144 weeks among participants with and without TDR (98% vs. 97%; as treated analysis). The data showed that of the 1240 patients who had shown confirmed suppression, 143 (11.5%) had 1 blip through week 144 with similar blip frequencies between treatment arms. Per study, an average of 1.3% of participants experienced blips. In 143 patients, total of 186 blip events were observed, 110 experienced a single blip and 33 experienced multiple blips. Of the 186 blips, 87 (46.8%) were low-level (50-199 c/mL) and 99 (53.2%) were 200 c/mL. Similarity was observed for proportions of participants with blips <200 c/mL or 200 c/mL. Most patients with blips 200 c/mL showed adherence 95% by pill count (69.2%), while those with blips <200 c/mL mostly showed adherence >95% (63.1%). Of participants without blips, 98.7% (1083/1097) showed HIV RNA <50 c/mL at week 144 or last visit versus, 91.0% (71/78) with blips 200 c/mL (p<0.01), or versus 96.9% (63/65) with blips <200 c/mL (P = 0.2). At week 144, 7 with blips 200 c/mL and HIV RNA 50 c/mL were on DTG-based regimens, and 6/7 had evidence of continued low adherence. Of 21 patients who underwent overall resistant analysis population, five patients showed blips [15] [27] [31] [34] .

Results from 1844, 1878, 4030 and 4449 trials achieved its primary endpoint of HIV-1 RNA<50 copies/mL at week 48 with a proportion of 92 percent (129/140), showing that Biktarvy in older adults maintained high rates of virologic suppression [17] [36] [40] [25] [24] .

Future Events

Expected Date Event Type Description Updated
30 Jun 2019 Trial Update Gilead Sciences plans a phase Ib trial for HIV-1-infection (Treatment-experienced) (PO) in June 2019 (PO, Tablet) (NCT03960645) (700307666) 01 Jul 2019
01 Jan 2019 Trial Update Gilead Sciences in collaboration with Janssen Pharmaceuticals plans the LAPTOP phase III trial for HIV-1 infections in Belgium, France, Germany, Ireland, Italy, Russia, Spain and United Kingdom (700300406), (NCT03696160) 29 Mar 2019
01 Sep 2018 Trial Update Gilead sciences plans the BIO trial for HIV-1 infections in Australia (ACTRN12618001340224p) 01 Jul 2019
31 Aug 2018 Trial Update Gilead Sciences plans the BRAAVE 2020 phase III trial for HIV-1 Infections in August 2018 (700298862), (NCT03631732) 28 Sep 2018
30 Jun 2018 Regulatory Status Gilead expects approval of bictegravir/emtricitabine/tenofovir alafenamide for HIV-1 infections in European Union by mid-2018 [4] 29 Jun 2018
30 Jun 2018 Trial Update Gilead Sciences plans a phase III trial for HIV and Hepatitis B infections (Treatment naive) in June 2018 (700296457), (NCT03547908) 14 Aug 2018
12 Feb 2018 Regulatory Status FDA assigns PDUFA action date of 12/02/2018 for bictegravir/emtricitabine/tenofovir alafenamide for HIV-1 infections (Treatment-naive, Treatment-experienced) [7] 08 Feb 2018
31 Jan 2018 Trial Update Gilead Sciences plans a phase IIIb trial for HIV-1 infections (NCT03405935) (700292558) 28 Mar 2018
30 Sep 2017 Regulatory Status Gilead Sciences announces it intention to submit MAA to EMA for HIV-1 infections in Q3 2017 [26] 30 Jan 2018
01 Jul 2017 Trial Update Gilead Sciences plans a phase III trial for HIV-1 infections (NCT03110380) 04 Jul 2017
30 Jun 2017 Regulatory Status Gilead Sciences announces it intention to submit NDA to US FDA for HIV-1 infections in Q2 2017 [26] 11 Aug 2017

Development History

Event Date Update Type Comment
18 Oct 2021 Phase Change - Marketed Launched for HIV-1 infections (In adolescents, In children) in USA (PO) [3] Updated 20 Oct 2021
18 Oct 2021 Phase Change - Registered Registered for HIV-1 infections (In adolescents, In children) in USA (PO) [3] Updated 20 Oct 2021
14 Sep 2021 Biomarker Update Biomarkers information updated Updated 17 Sep 2021
02 Jul 2021 Trial Update Gilead completes a phase-III clinical trial in HIV-1 infections (Treatment-naive) in the USA, Belgium, Canada, Dominican Republic, France, Germany, Italy, Puerto Rico, Spain, United Kingdom (PO) (NCT02607930) (EudraCT2015-004024-54) Updated 03 Aug 2021
21 Apr 2021 Trial Update Gilead Sciences completed a phase I pharmacokinetic trial in patients with HIV and latent TB co-infection in USA prior to March 2021 [49] Updated 21 Apr 2021
06 Mar 2021 Scientific Update Pooled efficacy and adverse events data from two phase III trial in HIV-1 infections presented at the 28th Conference on Retroviruses and Opportunistic Infections (CROI-2021) [32] Updated 03 May 2021
06 Mar 2021 Scientific Update Adverse events and pharmacokinetics data from a phase I trial in HIV infection presented at the 28th Conference on Retroviruses and Opportunistic Infections (CROI-2021) [49] Updated 21 Apr 2021
06 Mar 2021 Scientific Update Efficacy data from a phase III trial in HIV infection presented at the Conference on Retroviruses and Opportunistic Infections (CROI-2021) [16] Updated 21 Apr 2021
06 Mar 2021 Trial Update Gilead Sciences initiated a phase I pharmacokinetic trial in patients with HIV and latent TB co-infection in USA prior to March 2021 [49] Updated 21 Apr 2021
06 Mar 2021 Scientific Update Pooled efficacy data from phase III Study 1489 and Study 1490 presented at the 28th Conference on Retroviruses and Opportunistic Infections (CROI-2021) [15] Updated 12 Mar 2021
10 Feb 2021 Trial Update Gilead Sciences completes the phase III trial for HIV-1 infections (Treatment-experienced) in the USA, Austria, Canada, France, Germany and Puerto Rico (PO)(NCT03110380) Updated 05 Apr 2021
01 Feb 2021 Financial Update Credit Suisse financial data update Updated 14 Mar 2021
31 Dec 2020 Patent Information Gilead Sciences has patent protection for bictegravir/emtricitabine/tenofovir alafenamide in USA and European Union [58] Updated 28 Apr 2021
22 Oct 2020 Scientific Update Efficacy data from a phase III BRAAVE 2020 trial in HIV-1 infections released by Gilead Sciences [22] Updated 23 Oct 2020
21 Oct 2020 Scientific Update Pharmacodynamics data from preclinical trial in HIV-1 infections presented at IDWeek 2020 (IDW-2020) [55] Updated 14 Dec 2020
21 Oct 2020 Scientific Update Updated efficacy and safety data from the phase III BRAAVE 2020 trial in HIV-1 infections presented at IDWeek 2020 (IDW-2020) [21] Updated 14 Dec 2020
21 Oct 2020 Scientific Update Efficacy, pharmacokinetics and adverse events data from a phase III trial in HIV-1 infection presented at the IDWeek 2020 (IDW-2020) [38] Updated 11 Dec 2020
19 Aug 2020 Trial Update Gilead Sciences completes the BRAAVE 2020 phase III trial for in HIV-1 infections (Treatment-experienced) in USA (PO) (NCT03631732) Updated 20 Oct 2020
07 Jul 2020 Scientific Update Efficacy data from a phase III trial in HIV infections presented at the 23rd International AIDS Conference (AIDS 2020) [17] Updated 07 Jul 2020
04 Jul 2020 Scientific Update Pooled efficacy and adverse data from a phase III trial in HIV infections presented at the 23rd International AIDS Conference (AIDS 2020) [17] Updated 07 Jul 2020
29 May 2020 Trial Update Gilead Sciences completes a phase IIIb trial in HIV-1 infections (In the elderly) in United Kingdom, Belgium, Italy, France and Spain (PO) (NCT03405935) Updated 30 Jul 2020
10 Mar 2020 Scientific Update Efficacy and adverse events data from the phase III BRAAVE 2020 trial in HIV-1 infections released by Gilead Sciences [19] Updated 13 Mar 2020
08 Mar 2020 Scientific Update Efficacy data from the phase III BRAAVE 2020 trial in HIV-1 infections presented at the 27th Conference on Retroviruses and Opportunistic Infections (CROI-2020) [61] Updated 07 Apr 2020
08 Mar 2020 Phase Change - Preclinical Preclinical trials in HIV-1 infections (Prevention) in USA (PO) before March 2020 [56] Updated 06 Apr 2020
08 Mar 2020 Scientific Update Pharmacodynamics data from preclinical studies in HIV infections (Prevention) presented at the 27th Conference on Retroviruses and Opportunistic Infections (CROI-2020) [56] Updated 06 Apr 2020
08 Mar 2020 Scientific Update Pooled adverse events data from phase III Study 1489 and Study 1490 presented at the 27th Conference on Retroviruses and Opportunistic Infections (CROI-2020) [28] Updated 06 Apr 2020
08 Mar 2020 Scientific Update Safety and pharmacodynamics data from a phase I trial in HIV infections presented at the 27th Conference on Retroviruses and Opportunistic Infections (CROI-2020) [50] Updated 06 Apr 2020
08 Mar 2020 Scientific Update Safety, efficacy and pharmacodynamics data from a phase II/III trial in HIV-1 infections presented at the 27th Conference on Retroviruses and Opportunistic Infections (CROI-2020) [47] Updated 06 Apr 2020
08 Mar 2020 Trial Update Gilead Sciences completes a phase I trial in HIV infections before March 2020 [50] Updated 06 Apr 2020
08 Mar 2020 Scientific Update Pooled efficacy data from phase III Study 1489 and Study 1490 presented at the 27th Conference on Retroviruses and Opportunistic Infections (CROI-2020) [27] Updated 03 Apr 2020
01 Mar 2020 Trial Update Gilead Sciences initiates a phase I trial in HIV infections before March 2020 [50] Updated 06 Apr 2020
23 Dec 2019 Trial Update Gilead Sciences completes a phase I trial in HIV-1 infections (Treatment-experienced) in Australia, Belgium, Canada, Dominican Republic, France, Germany, Italy, Puerto Rico, Spain and United Kingdom (PO) (NCT02603107) (EudraCT2015-004011-20) Updated 04 Feb 2020
06 Nov 2019 Scientific Update Safety and efficacy data from the phase III (Study 1489 and Study 1490) in HIV-1 infections released by Gilead [62] Updated 25 Nov 2019
16 Aug 2019 Phase Change - Marketed Launched for HIV-1 infections (Treatment-experienced) in Canada (PO), prior to August 2019 [1] Updated 19 Aug 2019
16 Aug 2019 Phase Change - Marketed Launched for HIV-1 infections (Treatment-naive) in Canada (PO), prior to August 2019 [1] Updated 19 Aug 2019
09 Aug 2019 Phase Change - Registered Registered for HIV-1 infections (Treatment-experienced) in China (PO) [11] Updated 13 Aug 2019
09 Aug 2019 Phase Change - Registered Registered for HIV-1 infections (Treatment-naive) in China (PO) [11] Updated 13 Aug 2019
22 Jul 2019 Scientific Update Efficacy and safety data from two phase III trials in HIV-1 infections released by Gilead Sciences [37] Updated 24 Jul 2019
18 Jul 2019 Regulatory Status The US FDA approves labeling revisions to bictegravir/ emtricitabine/tenofovir alafenamide for expanding patient population to include HIV-1 infected pediatric patients [57] Updated 22 Jul 2019
08 Jul 2019 Phase Change - Marketed Launched for HIV-1 infections (Treatment-experienced) in Denmark, United Kingdom, Poland, Netherlands (PO) prior to July 2019 Updated 08 Jul 2019
08 Jul 2019 Phase Change - Marketed Launched for HIV-1 infections (Treatment-naive) in Denmark, United Kingdom, Poland, Netherlands (PO) prior to July 2019 Updated 08 Jul 2019
01 Jun 2019 Trial Update Gilead Sciences initiates a phase Ib trial for HIV-1-infection (Treatment-experienced) in USA (PO, Tablet) (NCT03960645) Updated 01 Jul 2019
23 May 2019 Trial Update Gilead Sciences plans a phase Ib trial for HIV-1-infection (Treatment-experienced) (PO) in June 2019 (PO, Tablet) (NCT03960645) Updated 01 Jul 2019
26 Mar 2019 Phase Change - Registered Registered for HIV-1 infections (Treatment-experienced) in Japan (PO) [12] Updated 29 Mar 2019
26 Mar 2019 Phase Change - Registered Registered for HIV-1 infections (Treatment-naive) in Japan (PO) [12] Updated 29 Mar 2019
06 Mar 2019 Scientific Update Efficacy data from three phase III trial (GS-US-380-1844, GS-US380-1878, GS-US-380-4030) in HIV infections released by Gilead Sciences [63] Updated 11 Mar 2019
06 Mar 2019 Scientific Update Updated efficacy data from a phase II/III trial (GS-US-380-1474) in HIV infections presented at the 26th Conference on Retroviruses and Opportunistic Infections (CROI-2019) [45] Updated 11 Mar 2019
05 Mar 2019 Trial Update Gilead Sciences in collaboration with Janssen Pharmaceuticals initiates enrolment in the LAPTOP phase III trial for HIV-1 infections in United Kingdom (NCT03696160) Updated 29 Mar 2019
10 Jan 2019 Trial Update Gilead Sciences completes a phase III trial in HIV-1 infection (Treatment experienced) in USA, Russia, Thailand, Puerto Rico, Uganda and Dominican Republic (PO) (NCT02652624) Updated 14 Jan 2019
30 Oct 2018 Scientific Update Updated efficacy and adverse events data from a phase III trial in HIV-1 infections released by Gilead Sciences [33] Updated 12 Feb 2019
29 Oct 2018 Phase Change - Marketed Launched for HIV-1 infections (Treatment-experienced) in Norway (PO) Updated 08 Jul 2019
29 Oct 2018 Phase Change - Marketed Launched for HIV-1 infections (Treatment-naive) in Norway (PO) Updated 08 Jul 2019
04 Oct 2018 Trial Update Gilead Sciences in collaboration with Janssen Pharmaceuticals plans the LAPTOP phase III trial for HIV-1 infections in Belgium, France, Germany, Ireland, Italy, Russia, Spain and United Kingdom , (NCT03696160) Updated 29 Mar 2019
03 Oct 2018 Scientific Update Updated efficacy and adverse events data from a phase III trial in HIV-1 infections released by Gilead Sciences [29] Updated 09 Oct 2018
03 Oct 2018 Phase Change - Registered Registered for HIV-1 infections (Treatment-experienced) in Hong Kong (PO) [13] Updated 05 Oct 2018
03 Oct 2018 Phase Change - Registered Registered for HIV-1 infections (Treatment-naive) in Hong Kong (PO) [13] Updated 05 Oct 2018
28 Aug 2018 Trial Update Gilead Sciences initiates enrolment in the BRAAVE 2020 phase III trial for in HIV-1 infections (Treatment-experienced) in the US (PO) (NCT03631732) Updated 28 Sep 2018
15 Aug 2018 Trial Update Gilead Sciences plans the BRAAVE 2020 phase III trial for HIV-1 Infections in August 2018 , (NCT03631732) Updated 28 Sep 2018
06 Aug 2018 Trial Update Gilead sciences plans the BIO trial for HIV-1 infections in Australia (ACTRN12618001340224p) Updated 01 Jul 2019
12 Jul 2018 Phase Change - Registered Registered for HIV-1 infections (Treatment-experienced) in Australia (PO) (TGA website, August 2018) Updated 10 Aug 2018
12 Jul 2018 Phase Change - Registered Registered for HIV-1 infections (Treatment-naive) in Australia (PO) (TGA website, August 2018) Updated 10 Aug 2018
12 Jul 2018 Phase Change - Preregistration Preregistration for HIV-1 infections (Treatment-experienced) in Canada (PO) before July 2018 [2] Updated 17 Jul 2018
12 Jul 2018 Phase Change - Preregistration Preregistration for HIV-1 infections (Treatment-naive) in Canada (PO) before July 2018 [2] Updated 17 Jul 2018
12 Jul 2018 Phase Change - Registered Registered for HIV-1 infections (Treatment-experienced) in Canada (PO) [2] Updated 17 Jul 2018
12 Jul 2018 Phase Change - Registered Registered for HIV-1 infections (Treatment-naive) in Canada (PO) [2] Updated 17 Jul 2018
25 Jun 2018 Phase Change - Registered Registered for HIV-1 infections (Treatment-experienced) in Liechtenstein, Iceland, Norway, European Union (PO) [8] Updated 29 Jun 2018
25 Jun 2018 Phase Change - Registered Registered for HIV-1 infections (Treatment-naive) in Liechtenstein, Iceland, Norway, European Union (PO) [8] Updated 29 Jun 2018
06 Jun 2018 Trial Update Gilead Sciences plans a phase III trial for HIV and Hepatitis B infections (Treatment naive) in June 2018 , (NCT03547908) Updated 14 Aug 2018
30 May 2018 Trial Update Gilead Sciences initiates enrolment in a phase III trial for HIV-1/HBV Co-Infection in the US and Puerto Rico (NCT03547908) Updated 29 Jun 2018
27 Apr 2018 Regulatory Status Committee for Medicinal Products for Human Use (CHMP) of the EMA recommends approval of bictegravir/emtricitabine/tenofovir alafenamide for HIV-1 infections in European Union [9] Updated 30 Apr 2018
05 Mar 2018 Scientific Update Efficacy and adverse events data from a phase III trial (Study 1844) in HIV-1 infections released by Gilead Sciences [35] Updated 09 Mar 2018
05 Mar 2018 Scientific Update Interim efficacy and adverse events data from a phase III trial in HIV-1 infections released by Gilead Sciences [42] Updated 08 Mar 2018
04 Mar 2018 Scientific Update Safety, efficacy and pharmacokinetics data from a phase II/III trial in HIV-1 infections presented at the 25th Conference on Retroviruses and Opportunistic Infections (CROI-2018) [44] Updated 23 Apr 2018
01 Mar 2018 Phase Change - Preregistration Preregistration for HIV-1 infections (Treatment-experienced) in Australia (PO) [14] Updated 10 Aug 2018
01 Mar 2018 Phase Change - Preregistration Preregistration for HIV-1 infections (Treatment-naive) in Australia (PO) [14] Updated 10 Aug 2018
01 Mar 2018 Phase Change - III Phase-III clinical trials in HIV-1 infections (In the elderly) in United Kingdom, Italy, France (PO) (NCT03405935) Updated 29 Jun 2018
01 Mar 2018 Phase Change - III Phase-III clinical trials in HIV-1 infections (In the elderly) in Belgium, Spain (PO) (NCT03405935) (EudraCT2017-003428-61) Updated 28 Mar 2018
28 Feb 2018 Regulatory Status Gilead expects approval of bictegravir/emtricitabine/tenofovir alafenamide for HIV-1 infections in European Union by mid-2018 [4] Updated 29 Jun 2018
27 Feb 2018 Phase Change - Marketed Launched for HIV-1 infections (Treatment-experienced) in USA (PO) [4] Updated 28 Feb 2018
27 Feb 2018 Phase Change - Marketed Launched for HIV-1 infections (Treatment-naive) in USA (PO) [4] Updated 28 Feb 2018
07 Feb 2018 Phase Change - Registered Registered for HIV-1 infections (Treatment-experienced, Treatment-naive) in USA and Puerto Rico (PO) - First global approval [5] Updated 13 Feb 2018
07 Feb 2018 Patent Information ViiV Healthcare files patent infringement litigation against Gilead Sciences over bictegravir in USA and Canada [59] Updated 12 Feb 2018
07 Feb 2018 Regulatory Status The approved US FDA label for bictegravir/emtricitabine/tenofovir alafenamide carries a black box warning regarding post treatment acute exacerbation of hepatitis B [5] Updated 08 Feb 2018
30 Jan 2018 Trial Update Gilead Sciences plans a phase IIIb trial for HIV-1 infections (NCT03405935) Updated 28 Mar 2018
04 Oct 2017 Scientific Update Pharmacokinetics and pharmacodynamics data from a phase I trial in HIV-1 infections (In volunteers) presented at the IDWeek 2017 (IDW-2017) [54] Updated 27 Oct 2017
04 Oct 2017 Scientific Update Safety and efficacy data from the phase III (Study 1878) trial in HIV-1 infections presented at the IDWeek 2017 [39] Updated 06 Oct 2017
10 Aug 2017 Regulatory Status FDA assigns PDUFA action date of 12/02/2018 for bictegravir/emtricitabine/tenofovir alafenamide for HIV-1 infections (Treatment-naive, Treatment-experienced) [7] Updated 08 Feb 2018
10 Aug 2017 Regulatory Status Bictegravir/emtricitabine/tenofovir alafenamide receives priority review status for HIV-1 infections (Treatment-naive, Treatment-experienced) in USA [7] Updated 11 Aug 2017
28 Jul 2017 Other Chemical structure information added Updated 28 Jul 2017
24 Jul 2017 Scientific Update Safety and efficacy data from the phase III (Study 1489 and Study 1490) in HIV-1 infections released by Gilead [30] Updated 27 Jul 2017
13 Jul 2017 Phase Change - Preregistration Preregistration for HIV-1 infections (Treatment-experienced) in European Union (PO) [10] Updated 17 Jul 2017
13 Jul 2017 Phase Change - Preregistration Preregistration for HIV-1 infections (Treatment-naive) in European Union (PO) [10] Updated 17 Jul 2017
13 Jul 2017 Regulatory Status EMA accepts and validates MAA for Bictegravir/emtricitabine/tenofovir alafenamide for HIV-1 infections (Treatment experienced, Treatment naive) for review [10] Updated 17 Jul 2017
13 Jun 2017 Phase Change - Preregistration Preregistration for HIV-1 infections (Treatment-experienced) in USA (PO) [6] Updated 24 Jun 2017
13 Jun 2017 Phase Change - Preregistration Preregistration for HIV-1 infections (Treatment-naive) in USA (PO) [6] Updated 24 Jun 2017
13 Jun 2017 Regulatory Status Gilead Sciences files NDA for treatment of adult patients with HIV-1 infections in USA [6] Updated 23 Jun 2017
12 Jun 2017 Trial Update Gilead Sciences initiates enrolment in a phase III trial for HIV-1 infections (Treatment-experienced) in Austria, Canada, France, Germany and Puerto Rico (PO) after June 2017 (NCT03110380) Updated 13 Feb 2018
12 Jun 2017 Trial Update Gilead Sciences initiates enrolment in the phase III trial for HIV-1 infections (Treatment-experienced) in USA (PO)(NCT03110380) Updated 04 Jul 2017
30 May 2017 Regulatory Status Gilead Sciences announces it intention to submit MAA to EMA for HIV-1 infections in Q3 2017 [26] Updated 30 Jan 2018
30 May 2017 Regulatory Status Gilead Sciences announces it intention to submit NDA to US FDA for HIV-1 infections in Q2 2017 [26] Updated 11 Aug 2017
30 May 2017 Scientific Update Efficacy and adverse events data from four phase III trials in HIV-1 infections released by Gilead Sciences [26] Updated 08 Jun 2017
18 Apr 2017 Trial Update Gilead Sciences plans a phase III trial for HIV-1 infections (NCT03110380) Updated 04 Jul 2017
01 Sep 2016 Phase Change - II/III Phase-II/III clinical trials in HIV-1 infections (In adolescents, In children) in Uganda (PO) (NCT02881320) Updated 26 Jul 2017
01 Sep 2016 Phase Change - II/III Phase-II/III clinical trials in HIV-1 infections (In adolescents, In children) in Thailand and South Africa (PO) (NCT02881320) Updated 18 Apr 2017
01 Sep 2016 Phase Change - II/III Phase-II/III clinical trials in HIV-1 infections (In adolescents, In children) in USA (PO) (NCT02881320) Updated 21 Oct 2016
01 Feb 2016 Phase Change - III Phase-III clinical trials in HIV-1 infections (Treatment-experienced) in Uganda, Thailand, Russia (PO) (NCT02652624) Updated 13 Feb 2018
01 Feb 2016 Trial Update Gilead Sciences initiates enrolment in a phase III trial for HIV-1 infections (Treatment-experienced) in Dominican Republic and Puerto Rico (NCT02652624) Updated 13 Feb 2018
01 Feb 2016 Trial Update Gilead Sciences initiates enrollment in a phase III trial for HIV-1 infection (Treatment-experienced) in USA (PO) (NCT02652624) Updated 26 Feb 2016
30 Jan 2016 Trial Update Gilead Sciences plans a phase III trial for HIV-1 infection (Treatment-experienced) in USA, Russia, Thailand, Uganda and Dominican Republic (PO) (NCT02652624) Updated 30 Jan 2016
30 Nov 2015 Trial Update Gilead Sciences initiates enrolment in a phase III trial for HIV-1 infections (Treatment-experienced) in USA (PO) (NCT02603107) Updated 16 Dec 2015
13 Nov 2015 Phase Change - III Phase-III clinical trials in HIV-1 infections (Treatment-naive) in Belgium, Canada, Dominican Republic, France, Germany, Italy, Puerto Rico, Spain, United Kingdom (PO) after November 2015 (NCT02607930) Updated 08 Jun 2017
11 Nov 2015 Phase Change - III Phase-III clinical trials in HIV-1 infections (Treatment-naive) in Gabon, Australia (PO) after November 2015 (NCT02607956) Updated 08 Jun 2017
11 Nov 2015 Trial Update Gilead initiates a phase III trial for HIV-1 infections (Treatment-naive) in Dominican Republic, France, Germany, Canada, Belgium, Italy, Puerto Rico, Spain and United Kingdom (PO) after November 2015 (NCT02607956) Updated 08 Jun 2017
11 Nov 2015 Trial Update Gilead Sciences initiates enrolment in a phase III trial for HIV-1 infections (Treatment-experienced) in Australia, France, Germany, Canada, Belgium, Italy, Puerto Rico, Spain and United Kingdom (PO) after November 2015 (NCT02603120) Updated 08 Jun 2017
01 Nov 2015 Phase Change - III Phase-III clinical trials in HIV-1 infections (Treatment-experienced) in Australia, Belgium, Canada, Dominican Republic, France, Germany, Italy, Puerto Rico, Spain and United Kingdom (PO) (NCT02603107) after November 2015 Updated 18 Jul 2016
01 Nov 2015 Phase Change - III Phase-III clinical trials in HIV-1 infections (Treatment-experienced) in USA (PO) Updated 07 Dec 2015
01 Nov 2015 Phase Change - III Phase-III clinical trials in HIV-1 infections (Treatment-naive) in USA (PO) (NCT02607930) Updated 23 Nov 2015
01 Nov 2015 Trial Update Gilead initiates enrolment in a second phase III trial for HIV-1 infections (Treatment-naive) in USA (NCT02607956) Updated 23 Nov 2015

References

  1. Quebec Provides Access to Biktarvy(Rm) for the Treatment of HIV.

    Media Release
  2. Gilead Receives Approval in Canada for BIKTARVY(TM) (bictegravir, emtricitabine, tenofovir alafenamide) for the Treatment of HIV-1 Infection.

    Media Release
  3. U.S. Food and Drug Administration Approves Expanded Indication of Gileads Biktarvy(Rm) for Treatment of HIV-1 in Pediatric Populations.

    Media Release
  4. U.S. Food and Drug Administration Approves Gilead's Biktarvy(R) (Bictegravir, Emtricitabine, Tenofovir Alafenamide) for Treatment of HIV-1 Infection.

    Media Release
  5. Gilead Submits New Drug Application to U.S. Food and Drug Administration for Fixed-Dose Combination of Bictegravir, Emtricitabine and Tenofovir Alafenamide for HIV Treatment.

    Media Release
  6. Gilead Announces U.S. FDA Priority Review Designation for Fixed-Dose Combination of Bictegravir, Emtricitabine and Tenofovir Alafenamide for Treatment of HIV.

    Media Release
  7. European Commission Grants Marketing Authorization for Gilead's Biktarvy(R) (Bictegravir, Emtricitabine, Tenofovir Alafenamide) for the Treatment of HIV-1 Infection.

    Media Release
  8. European CHMP Adopts Positive Opinion for Gileads Biktarvy(R) (Bictegravir, Emtricitabine, Tenofovir Alafenamide).

    Media Release
  9. European Medicines Agency Validates Gileads Marketing Application for Fixed-Dose Combination of Bictegravir, Emtricitabine and Tenofovir Alafenamide for Treatment of HIV.

    Media Release
  10. China National Medical Products Administration Approves Biktarvy(Rm) (Bictegravir, Emtricitabine and Tenofovir Alafenamide) for Treatment of HIV-1 Infection.

    Media Release
  11. Japan's Ministry of Health, Labour and Welfare Approves Gilead's Biktarvy(R) (Bictegravir, Emtricitabine and Tenofovir Alafenamide) for Treatment of HIV-1 Infection.

    Media Release
  12. Hong Kong Department of Health Approves Biktarvy(R) (bictegravir, emtricitabine, tenofovir alafenamide).

    Media Release
  13. Biktarvy(Rm) Demonstrates High Efficacy and Durable Viral Suppression in Treatment-Nave Adults in Four-Year Data Presented at CROI.

    Media Release
  14. Acosta RK, Chen GQ, Chang S, Martin R, Wang X, Huang H, et al. Hiv with Transmitted Drug Resistance is Durably Suppressed by B/F/Taf at Week 144. CROI-2021 2021; abstr. 430.

    Available from: URL: http://www.croiconference.org/
  15. New Findings on Gileads Biktarvy(Rm) Presented at AIDS 2020: Virtual Include Positive Switch Data in Older Adults.

    Media Release
  16. An Open-Label, Multi-Centre, Randomised Study to Investigate Integrase Inhibitor Versus Boosted Protease Inhibitor Antiretroviral Therapy for Patients With Advanced HIV Disease

    ctiprofile
  17. New Data on Gileads Biktarvy(Rm) Presented at CROI 2020, Including Data in Black Americans and Older Adults.

    Media Release
  18. A Phase 3b, Multicenter, Open-Label Study to Evaluate Switching From a Regimen of Two Nucleos(t)Ide Reverse Transcriptase Inhibitors (NRTI) Plus a Third Agent to a Fixed Dose Combination (FDC) of Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF), in Virologically-Suppressed, HIV-1 Infected African American Participants

    ctiprofile
  19. Hagins DP, Kumar PN, Saag M, Wurapa AK, Brar I, Berger D, et al. Week 48 Outcomes from the BRAAVE 2020 Study: A Randomized Switch to B/F/TAF in African American Adults with HIV. IDW-2020 2020; abstr. 1046.

    Available from: URL: https://www.eventscribe.net/2020/IDWeek/ajaxcalls/PosterInfo.asp?efp=VFhWUUpXVFA2ODg4&PosterID=290993&rnd=0.1955273
  20. Gilead Announces New Data on Biktarvy(Rm) for the Treatment of HIV in Black Americans.

    Media Release
  21. A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Fixed Dose Combination of Bictegravir/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir + Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment Naïve, HIV-1 and Hepatitis B Co-Infected Adults

    ctiprofile
  22. A Phase 3b, Multicenter, Open-Label Study to Evaluate Switching From an Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Fixed-Dose Combination Regimen or a Tenofovir Disoproxil Fumarate Containing Regimen to Fixed-Dose Combination of Bictegravir/Emtricitabine/Tenofovir Alafenamide in Elderly, Virologically-Suppressed, HIV-1 Infected Subjects Aged ≥ 65 Years

    ctiprofile
  23. A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Switching From a Regimen of Dolutegravir and Either Emtricitabine/Tenofovir Alafenamide or Emtricitabine/Tenofovir Disoproxil Fumarate to a Fixed Dose Combination of Bictegravir/ Emtricitabine/Tenofovir Alafenamide in HIV-1 Infected Subjects Who Are Virologically Suppressed

    ctiprofile
  24. Gileads Investigational Fixed-Dose Combination of Bictegravir, Emtricitabine and Tenofovir Alafenamide for the Treatment of HIV-1 Meets Primary Endpoint in Four Phase 3 Studies.

    Media Release
  25. Acosta RK, Andreatta K, D'Antoni ML, Collins SE, Martin H, White KL. HIV VIRAL BLIPS IN ADULTS TREATED WITH InSTI-BASED REGIMENS THROUGH 144 WEEKS. CROI-2020 2020; abstr. 540.

    Available from: URL: http://www.croiconference.org/sessions/hiv-viral-blips-adults-treated-insti-based-regimens-through-144-weeks
  26. Mills A, Gupta SK, Brinson C, Workowski K, Clarke A, Antinori A, et al. -- please add a title --. CROI-2020 2020; abstr. 477.

    Available from: URL: http://www.croiconference.org/sessions/144-week-efficacy-and-safety-bftaf-treatment-naive-adults-%E2%89%A550-yrs
  27. Gilead Announces 96-Week Results From Phase 3 Study of Biktarvy(R)(Bictegravir, Emtricitabine, Tenofovir Alafenamide) for the Treatment of HIV-1 in Adults New to HIV Therapy.

    Media Release
  28. Gilead Announces Phase 3 Results for Investigational Fixed-Dose Combination of Bictegravir, Emtricitabine and Tenofovir Alafenamide for Treatment of HIV.

    Media Release
  29. A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of GS-9883/Emtricitabine/Tenofovir Alafenamide Versus Abacavir/Dolutegravir/Lamivudine in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

    ctiprofile
  30. Workowski K, Orkin C, Sax P, Hagins D, Koenig E, Stephens J, et al. 4-Year Outcomes of B/F/Taf in Treatment-Naive Adults. CROI-2021 2021; abstr. 415.

    Available from: URL: http://www.croiconference.org/
  31. Gilead Announces 96-Week Results From Phase 3 Study of Biktarvy(Rm) (Bictegravir, Emtricitabine, Tenofovir Alafenamide) for the Treatment of HIV-1 in Adults New to HIV Therapy- 30 October 2018.

    Media Release
  32. A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of GS-9883/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir + Emtricitabine/Tenofovir Alafenamide in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

    ctiprofile
  33. Gilead Presents Results from Phase 3 Study Evaluating Patients Who Switched to Biktarvy(R) (Bictegravir, Emtricitabine and Tenofovir Alafenamide) from Regimen Containing Abacavir, Dolutegravir and Lamivudine.

    Media Release
  34. A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Switching From a Regimen of Dolutegravir and ABC/3TC, or a Fixed Dose Combination (FDC) of ABC/DTG/3TC to a FDC of GS-9883/F/TAF in HIV-1 Infected Subjects Who Are Virologically Suppressed

    ctiprofile
  35. Gilead Presents New Data on Biktarvy(Rm) for the Treatment of HIV in Women and in Virologically Suppressed Patients With Known Resistance.

    Media Release
  36. Brar I, Ruane P, Ward D, Molina J-m, Mills A, Berhe M, et al. Long-term Follow-up After a Switch to Bictegravir, Emtracitabine, Tenofovir Alafenamide from Dolutegravir, Abacavir, Lamivudine. IDW-2020 2020; abstr. 1028.

    Available from: URL: https://www.eventscribe.net/2020/IDWeek/ajaxcalls/PosterInfo.asp?efp=VFhWUUpXVFA2ODg4&PosterID=292340&rnd=0.8797188
  37. Gilead Presents Results From Phase 3 Study Evaluating Patients Who Switched to Investigational Fixed-Dose Combination of Bictegravir, Emtricitabine and Tenofovir Alafenamide From Boosted Protease Inhibitor-Based Regimens.

    Media Release
  38. A Phase 3, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Switching From Regimens Consisting of Boosted Atazanavir or Darunavir Plus Either Emtricitabine/Tenofovir or Abacavir/Lamivudine to GS-9883/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV-1 Infected Adults

    ctiprofile
  39. A Phase 3, Randomized, Open Label Study to Evaluate the Safety and Efficacy of Switching to a Fixed Dose Combination (FDC) of GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/F/TAF) From Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Alafenamide (E/C/F/TAF), Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate (E/C/F/TDF) or Atazanavir + Ritonavir + Emtricitabine/Tenofovir Disoproxil Fumarate (ATV+RTV+FTC/TDF) in Virologically Suppressed HIV-1 Infected Women

    ctiprofile
  40. Gilead Presents Data From Phase 3 Study Evaluating Women Who Switched to Biktarvy(R) (Bictegravir, Emtricitabine and Tenofovir Alafenamide) From a Boosted Protease Inhibitor-Based Regimen or Boosted Elvitegravir-Containing Regimen.

    Media Release
  41. A Phase 2/3, Open-Label Study of the Pharmacokinetics, Safety, and Antiviral Activity of the GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/F/TAF) Fixed Dose Combination (FDC) in HIV-1 Infected Adolescents and Children

    ctiprofile
  42. Gaur A, Rodriguez C, McGrath EJ, Hellstrom E, Liberty A, Natukunda E, et al. Bictegravir/Ftc/Taf Single-Tablet-Regimen in Adolescents: Week 24 Results. CROI-2018 2018; abstr. 844.

    Available from: URL: http://www.croiconference.org/sessions/bictegravirftctaf-single-tablet-regimen-adolescents-week-24-results
  43. Gilead Presents New Data on Biktarvy(Rm) (Bictegravir, Emtricitabine and Tenofovir Alafenamide) and TAF-Based Regimens for the Treatment of HIV-1 in Children, Older Adults and Women.

    Media Release
  44. Gaur A, Cotton M, Rodriguez C, McGrath EJ, Hellstrom E, Liberty A, et al. Bictegravir/Ftc/Taf Single-Tablet Regimen in Adolescents & Children: Week 48 Results. CROI-2019 2019; abstr. 46.

    Available from: URL: http://www.croiconference.org/sessions/bictegravirftctaf-single-tablet-regimen-adolescents-children-week-48-results
  45. Rodriguez C, Chokephaibulkit K, Liberty A, Strehlau R, Van Zyl R, Kosalaraksa P, et al. -- please add a title --. CROI-2020 2020; abstr. 840.

    Available from: URL: http://www.croiconference.org/sessions/safety-pk-and-efficacy-low-dose-bftaf-children-%E2%89%A52-years-old-living-hiv
  46. A Phase 1‚ open-label‚ 3-period‚ fixed sequence study analysing drug interactions with Bictegravir/emtricitabine/tenofovir-alafenamide in combination with Rifapentine

    ctiprofile
  47. Arora P, Collins SE, Martin H, Zhang X, Mak L, Ling J, et al. Drug Interactions with Once-Daily B/F/Taf in Combination with Once-Weekly Rifapentine. CROI-2021 2021; abstr. 369.

    Available from: URL: http://www.croiconference.org/
  48. Majeed SR, German P, West SK, Xiang SS, Xiao D, Keeney M, et al. B/F/TAF LOW-DOSE TABLET RELATIVE BIOAVAILABILITY IN HVs AND PK IN CHILDREN WITH HIV. CROI-2020 2020; abstr. 841.

    Available from: URL: http://www.croiconference.org/sessions/bftaf-low-dose-tablet-relative-bioavailability-hvs-and-pk-children-hiv
  49. A phase 1 randomized crossover study of Bictegravir/emtricitabine/tenofovir alafenamide low dose tablet relative to bioavailability in Healthy adult volunteers and pharmacokinetics in children with HIV

    ctiprofile
  50. A Phase 1b, Open-label Study to Evaluate the PK, Safety and Efficacy of B/F/TAF in HIV-1 Infected, Virologically Suppressed, Pregnant Women in Their Second and Third Trimesters

    ctiprofile
  51. A study evaluating the effect of Bictegravir/emtricitabine/tenofovir alafenamide on the pharmacokinetics of metformin in healthy subjects.

    ctiprofile
  52. Custodio J, West S, Yu A, Martin H, Graham H, Quirk E, et al. Lack of Clinically Relevant Effect of Bictegravir (BIC, B) on Metformin (MET) Pharmacokinetics (PK) and Pharmacodynamics (PD). IDW-2017 2017; abstr. 1386.

    Available from: URL: https://idsa.confex.com/idsa/2017/webprogram/Paper65384.html
  53. Mulato A, Acosta RK, Yant SR, Cihlar T, White KL. Forgiveness of BIC/FTC/TAF: In Vitro Simulations of Intermittent Poor Adherence Find Limited HIV-1 Breakthrough and High Barrier to Resistance. IDW-2020 2020; abstr. 1448.

    Available from: URL: https://www.eventscribe.net/2020/IDWeek/ajaxcalls/PosterInfo.asp?efp=VFhWUUpXVFA2ODg4&PosterID=291437&rnd=0.9868616
  54. Bekerman E, Cox SW, McCallister S, Cihlar T, Callebaut C. Bic/Ftc/Taf Postexposure Prophylaxis Protects Macaques Against Rectal Shiv Infection. CROI-2020 2020; abstr. 87.

    Available from: URL: http://www.croiconference.org/sessions/bicftctaf-postexposure-prophylaxis-protects-macaques-against-rectal-shiv-infection
  55. Gilead to Present New Data on HIV Prevention, Treatment and Cure Research at IAS 2019.

    Media Release
  56. Gilead Sciences_SEC_Dec 2020. Internet-Doc 2021;.

    Available from: URL: https://www.sec.gov/ix?doc=/Archives/edgar/data/882095/000088209521000008/gild-20201231.htm
  57. ViiV Healthcare files patent infringement litigation against Gilead Sciences Inc. over bictegravir.

    Media Release
  58. AHF to Appeal Gilead AIDS Drug Patent Case.

    Media Release
  59. Andreatta K, D'Antoni ML, Chang S, Martin R, Blair C, Collins SE, et al. Preexisting Resistance and B/F/Taf Switch Efficacy in African Americans. CROI-2020 2020; abstr. 509.

    Available from: URL: http://www.croiconference.org/sessions/preexisting-resistance-and-bftaf-switch-efficacy-african-americans
  60. Gileads Biktarvy Maintained High Efficacy With No Cases of Treatment-Emergent Resistance Through Three Years in Phase 3 HIV Clinical Trials.

    Media Release
  61. Gilead Presents Data on Biktarvy(Rm) (Bictegravir, Emtricitabine and Tenofovir Alafenamide) in Virologically Suppressed Adults, Including Those With Pre-Existing NRTI Resistance.

    Media Release
  62. A Randomized, Double-Blind Study of the Safety and Efficacy of GSK1349572 Plus Abacavir/Lamivudine Fixed-Dose Combination Therapy Administered Once Daily Compared to Atripla Over 96 Weeks in HIV-1 Infected Antiretroviral Therapy Naive Adult Subjects

    ctiprofile
Back to top