Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials

Abstract

Session: P-24. Clinical Trials Background: VIR-2482 is a fully human immunoglobulin G1(IgG) monoclonal antibody (mAb) directed against a highly-conserved epitope in the influenza A hemagglutinin stem region and is in clinical development for the prevention of influenza A illness. The Fc region of VIR-2482 has been modified to provide an extended half-life.Methods: This is a randomized, placebo-controlled, Phase 1/2 study of VIR-2482 administered intramuscularly (IM) to healthy adult volunteers aged 18-64 years old who have not received a current influenza vaccine. The Phase 1 portion of the study will evaluate the safety, tolerability, pharmacokinetic (PK), and immunogenicity profile of VIR-2482 following single (Part A) or multiple doses (Part B). The Phase 2 study will evaluate the efficacy of VIR-2482 in the prevention of influenza A illness as well as safety, tolerability, and PK. Part A is ongoing and consists of four single dose cohorts (N=25/cohort) randomized (4:1) to a single dose of VIR-2482 or placebo at 60, 300, 1200, or 1800 mg. Safety, tolerability, PK and immunogenicity will be evaluated for at least 52 weeks post-dose.Results: In Part A, all 100 subjects received a single dose of VIR-2482 (N=80) or placebo (N=20). Preliminary blinded safety data for all cohorts and PK data for the 300 and 1200 mg cohorts are reported here. Dosing was well tolerated; 6% (6/100) of subjects experienced mild injection site reactions, which generally resolved within 48 hrs. Through 12 weeks post-dosing, the majority (124/126; 98.4%) of adverse events (AEs) were mild to moderate in nature, no serious AEs were reported, and no subjects discontinued due to an AE. Based on available data, exposure (C max and AUC) between 300 and 1200 mg of VIR-2482 increased in a dose proportional manner. The PK profile of VIR-2482 is consistent with a half-life extended IgG.Conclusion: Based on available data, VIR-2482 has been well tolerated following single IM doses of up to 1800 mg in healthy subjects. The preliminary PK profile of VIR-2482 enables once per season dosing. Overall, these data support initiation of a Phase 2 study to evaluate efficacy of VIR-2482 for the prevention of influenza A illness.

Evaluation of treatment simplification strategies in patients living with HIV with multi-drug resistance

“…1 , 10 This combination was often selected due to favorable tolerability profile of the BIC/FTC/TAF component, ability to retain partial NRTI activity in the patients for which it was prescribed, and due to the high barrier to resistance of bictegravir. 11 A pooled analysis of phase 3 clinical trial data by D’Antoni et al 11 found that a small cohort of patients with primary INSTI resistance achieved or maintained virologic suppression through 48 weeks of BIC/FTC/TAF treatment. Pre-existing INSTI mutations were detected in 20 of the 1907 participants, and all but one of these 20 participants was virologically suppressed at baseline.…”

“…11 A pooled analysis of phase 3 clinical trial data by D'Antoni et al Antoni et al11 reinforced our confidence in utilizing BIC/FTC/TAF as part of our simplification strategies. While there is limited guidance regarding bictegravir use in treatmentexperienced patients with drug resistance and in combination with other antiretroviral agents, we feel that our experience could help guide clinicians when multi-class combinations are needed with efforts to reduce pill burden.…”

Bictegravir/Emtricitabine/Tenofovir Alafenomide for the Treatment of HIV/Hepatitis B Virus Co-infection in Patients with Cancer and Transplant Recipients

“…16 Bictegravir/emtricitabine/tenofovir alafenamide in people with HIV who have underlying genotypic resistance In one study of individuals who had pre-existing INSTI resistance mutations with one primary INSTI-resistant substitution, including E92G, Y143C/H, S147G, Q148H/K/R, N155S or R263K, and some with secondary substitutions, 19 out of 20 individuals who were virologically suppressed successfully maintained virologic suppression when switched to BIC/FTC/TAF. 18 Additionally, BIC/FTC/TAF has been shown to be effective in individuals with NRTI-resistance associated mutations. In a study of PWH, of whom almost half carried the M184V/I resistance mutation and 21 out of 29 had more than one NRTI-resistance associated mutation, 49 out of 50 PWH had undetectable viral loads after over 18 months on treatment with BIC/FTC/ TAF.…”

Attitudes towards participating in research involving digital pill systems to measure oral HIV pre-exposure chemoprophylaxis: a cross-sectional study among men who have sex with men with substance use in the USA

“…Injectable formulations of PrEP, notably long-acting cabotegravir, have recently been found in randomised controlled trials to be efficacious for preventing HIV acquisition 11. Despite this, there have been concerns regarding new models of adherence with long-acting PrEP, and the spectre for potential integrase-inhibitor resistance in the setting of missed acute HIV infection with starting long-acting PrEP or resistance surrounding early stoppage of injectable PrEP 12 13. Additionally, certain patient populations may not accept a long-acting injectable PrEP formulation, or may experience adverse events at the injection site that may limit their use 14.…”