Drug Database: Albuvirtide

Pharmacology

Pharmacology

Mechanism of Action

Fusion inhibitor. Albuvirtide is a peptide derived from the C-terminal heptad repeat sequence of HIV-1 gp41 and modified to contain a single 3-maleimimidopropionic acid (MPA) group. Albuvirtide prevents HIV replication by binding to the HIV-1 gp41 env protein and inhibiting the formation of a six-helix bundle structure (6-HB) in gp41, which is necessary for fusion of the viral and cellular membranes. In vivo, albuvirtide irreversibly conjugates with serum albumin, allowing for an extended peptide half-life. Albuvirtide has demonstrated in vitro activity against various HIV-1 strains and certain variants that are resistant to enfuvirtide (Fuzeon).^4–6

In addition to being developed as a once-weekly injectable treatment for HIV, albuvirtide has also been studied as an agent for HIV post-exposure prophylaxis (PEP).^7,8

Half-life (T_½)

In a parallel group study of albuvirtide (single escalating doses of 20 to 640 mg and multiple doses of 160 mg or 320 mg) administered via intravenous (IV) injection in treatment-naive participants, the albuvirtide plasma half-life was 10 to 13 days.⁹

Metabolism/Elimination

Albuvirtide does not undergo metabolism by CYP enzymes.⁸

Resistance

The TALENT study is a Phase 3 trial (NCT02369965) that evaluated albuvirtide plus lopinavir/ritonavir versus lopinavir/ritonavir plus two NRTIs in treatment-experienced participants. At Week 48, 6% of participants in the albuvirtide group and 8% of participants in the comparator group had virological failure (HIV RNA levels at or above 400 copies/mL). Among the 11 albuvirtide-treated participants with virological failure, no gp41 resistance-associated mutations were detected.¹⁰

Select Clinical Trials

Select Clinical Trials

Study Identifier: ChiCTR-TRC-13003140

Sponsor: Frontier Biotechnologies Co., Ltd
Phase: 2
Status: This study has been completed.
Study Purpose: The purpose of this open-label trial was to evaluate 1) the drug-drug interaction between albuvirtide and lopinavir/ritonavir and 2) the short-term safety and efficacy of albuvirtide plus lopinavir/ritonavir.
Study Population:

• Participants were treatment-naive adults with HIV.
• Participants had HIV RNA between 5,000 and 1,000,000 copies/mL and CD4 counts >350 cells/mm³.⁵

Selected Study Results: Results published in AIDS Research and Therapy (2016) showed that there was little to no drug-drug interaction between albuvirtide and lopinavir/ritonavir. Additionally, albuvirtide combined with lopinavir/ritonavir was safe and effective in reducing viral load levels, with the higher albuvirtide dose tested having greater anti-HIV activity than the lower albuvirtide dose tested.⁵

Study Identifiers: TALENT; NCT02369965

Sponsor: Frontier Biotechnologies Inc.
Phase: 3
Status: This study has been completed.
Study Purpose: The purpose of this 48-week open-label trial was to compare the efficacy of albuvirtide plus lopinavir/ritonavir to two NRTIs plus lopinavir/ritonavir.
Study Population:

• Participants were children and adults (age 16 to 60 years) with HIV and who had treatment failure while on a standard first-line ART regimen. Participants had received previous ART with NRTIs/NNRTIs for more than 6 months.
• Participants had HIV RNA ≥1,000 copies/mL.¹¹

Selected Study Results: Results presented at IAS 2021 showed that albuvirtide plus lopinavir/ritonavir was noninferior to two NRTIs plus lopinavir/ritonavir in suppressing viral load in participants who had treatment failure on standard first-line ART.¹⁰
Additional Published Material:

• Chin Med J (Engl) article, 2020: Efficacy and safety of the long-acting fusion inhibitor albuvirtide in antiretroviral-experienced adults with human immunodeficiency virus-1: interim analysis of the randomized, controlled, phase 3, non-inferiority TALENT study

Study Identifier: NCT03719664

Sponsor: Frontier Biotechnologies Inc.
Phase: 2
Status: The status of this study is unknown.
Study Purpose: The purpose of this open-label study is to establish the optimal dosage of a two-drug regimen consisting of albuvirtide plus the bNAb 3BNC117 and evaluate the safety and efficacy of this regimen as maintenance therapy.
Study Population:

• Participants are adults with HIV who have been on an oral ART regimen for the past 24 weeks prior to study entry. Participants have been on a stable ART regimen (with exceptions) and have at least two potential alternative antiretroviral drug options available.
• Participants have HIV RNA <50 copies/mL at screening and have had HIV RNA <50 copies/mL in the past 24 weeks prior to screening.
• Participants have CD4 counts >300 cells/mm³ at screening.¹²

Study Identifier: NCT04819347

Sponsor: Frontier Biotechnologies Inc.
Phase: 2
Status: The status of this study is unknown.
Study Purpose: The purpose of this open-label study is to evaluate the safety of combination therapy with albuvirtide plus 3BNC117 and determine whether this combination can control viral load levels after an analytical treatment interruption of ART .
Study Population:

• Participants are adults with HIV on a stable ART regimen who initiated ART either within 6 months of primary HIV infection (cohort 1) or after 6 months of primary HIV infection (cohort 2).
• Participants have had HIV RNA <50 copies/mL for at least 12 months prior to screening and have HIV RNA <20 copies/mL at screening.
• Participants have CD4 counts >500 cells/mm³.¹³

Study Identifier: NCT04560569

Sponsor: Frontier Biotechnologies Inc.
Phase: 2
Status: The status of this study is unknown.
Study Purpose: The purpose of this open-label study is to evaluate the safety and efficacy of combination therapy with albuvirtide plus 3BNC117 in participants with multidrug-resistant HIV.
Study Population:

• Participants are adults with HIV who have received ART for at least 6 months. Participants have been on a failing ART regimen for at least 8 weeks prior to screening or had treatment failure within the past 8 weeks of screening and are off therapy.
• Participants have HIV that is resistant to at least one ARV drug from at least three different ARV drug classes and have difficulty in constructing a viable suppressive regimen. Participants must have at least one potential approved ARV drug available which can be used as part of an optimized background regimen.
• Participants have had HIV RNA >200 copies/mL within the last 3 months prior to screening and have HIV RNA ≥1,000 copies/mL at screening.¹⁴

Study Identifier: ChiCTR2100053311

Sponsor: Frontier Biotechnologies Inc.
Phase: 4
Status: This study has been completed.
Study Purpose: The purpose of this open-label study was to evaluate the effect of intensive albuvirtide treatment on immune function in individuals with incomplete immune reconstitution on suppressive ART.
Study Population:

• Participants were adults with HIV who had incomplete immune reconstitution while receiving continuous ART.
• Participants had HIV RNA <50 copies/mL.
• Participants had CD4 counts <500 cells/mm³ (5 years on ART) or <200 cells/mm³ (2–5 years on ART).^15,16

Selected Study Results: Results presented at EACS 2023 showed that after 12 weeks of treatment, 35% of the participants in the intensive albuvirtide treatment group had at least a 100 cell/mm³ increase in their CD4 counts from baseline. In comparison, only 10% of the participants in the control group had immunological improvement from baseline.¹⁶

Adverse Events

Adverse Events

ChiCTR-TRC-13003140

In this Phase 2 trial involving treatment-naive adults who received albuvirtide (160 mg or 320 mg) plus lopinavir/ritonavir, 10 participants were randomized to each of the two dosing groups. No serious adverse events (SAEs) occurred during the trial. In the 160 mg dosing group, eight adverse events (AEs) occurred among seven participants, while in the 320 mg dosing group, nine AEs occurred among eight participants. The AEs were all mild and mainly included hypertriglyceridemia, diarrhea, nausea, and rash. In each dosing group, six of the AEs were considered albuvirtide-related. None of the participants had injection site reactions.⁵

TALENT (NCT02369965)

In this Phase 3 study, 418 participants who had experienced first-line ARV treatment failure were enrolled to receive either albuvirtide plus lopinavir/ritonavir or two NRTIs plus lopinavir/ritonavir. The Week 48 safety analysis included data from 401 participants who had receieved at least one dose of study drug and found a similar overall safety profile between both study arms. Two participants in each group discontinued treatment due to AEs. Drug-related AEs occurred in 64.1% of partcipants in the albuviritde group and in 61.7% of participants in the comparator group. SAEs occurred in 6.2% and 5.8% of participants in the albuvirtide group and in the comparator group, respectively. None of the SAEs in the albuvirtide group were drug-related. No injection site reactions were reported with albuvirtide use. Common drug-related AEs and laboratory abnormalities across both groups included diarrhea, nausea, and increased triglycerides.^10,17

Drug Interactions

Drug Interactions

A study investigated the drug-drug interactions between albuvirtide (320 mg) and lopinavir/ritonavir (400/100 mg) in 10 participants with HIV. Results demonstrated that albuvirtide administered concomitantly with lopinavir/ritonavir has a negligible impact on albuvirtide exposure but decreases lopinavir/ritonavir exposures. Despite the drug-drug interaction, the researchers state that the lopinavir trough concentrations may still be adequate to maintain the clinical effectiveness of albuvirtide in combination with lopinavir/ritonavir.¹⁶

References

References

1. National Center for Biotechnology Information. PubChem Compound Summary for CID 134694278, Albuvirtide. Accessed February 26, 2024
2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Accessed February 26, 2024
3. Jeffreys R. The antiretroviral therapy pipeline 2023. Treatment Action Group Pipeline Report 2023. Accessed February 26, 2024
4. Chong H, Yao X, Zhang C, et al. Biophysical property and broad anti-HIV activity of albuvirtide, a 3-maleimimidopropionic acid-modified peptide fusion inhibitor. PLoS ONE. 2012;7(3). Accessed February 26, 2024
5. Zhang H, Jin R, Yao C, et al. Combination of long-acting HIV fusion inhibitor albuvirtide and LPV/r showed potent efficacy in HIV-1 patients. AIDS Res Ther. 2016;13. Accessed February 26, 2024
6. Saag M. New and investigational antiretroviral drugs for HIV infection: Mechanisms of action and early research findings. Top Antivir Med. 2012;20(5):162–167. Accessed February 26, 2024
7. Frontier Biotechnologies Inc. website. Products: AIKENING^TM. Accessed February 26, 2024
8. Nie J, Sun F, He X, et al. Tolerability and adherence of antiretroviral regimens containing long-acting fusion inhibitor albuvirtide for HIV post-exposure prophylaxis: a cohort study in China. Infect Dis Ther. 2021;10(4):2611-2623. doi:10.1007/s40121-021-00540-5. Accessed February 26, 2024
9. Wu H, Yao C, Lu R, et al. Albuvirtide, the first long-acting HIV fusion inhibitor, suppressed viral replication in HIV-infected adults. Abstract presented at: Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 9–12, 2012; San Francisco, CA. Abstract H-554. Accessed February 26, 2024
10. Wu H, Yao C, Zhang T, et al. Efficacy and safety of long acting HIV fusion inhibitor albuvirtide in treatment-experienced HIV-1 infected patients: Week 48 analysis from the randomized controlled phase 3 TALENT study. Poster presented at: IAS Conference on HIV Science; July 18-21, 2021; Virtual. Accessed February 26, 2024
11. Frontier Biotechnologies Inc. Efficacy and safety of albuvirtide for injection combined with LPV/r for treatment of HIV-1-infected patients failed first-line antiretroviral therapy. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 18, 2015. NLM Identifier: NCT02369965. Accessed February 26, 2024
12. Frontier Biotechnologies Inc. A Phase 2, multicenter, three-part study to establish the dosage, safety and antiviral activity of combination therapy with albuvirtide and 3BNC117 as long-acting maintenance therapy in virologically suppressed subjects with HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 22, 2018. NLM Identifier: NCT03719664. Accessed February 26, 2024
13. Frontier Biotechnologies Inc. The Phase 2, two arms, one site, safety and antiviral activity of combination therapy with albuvirtide and 3BNC117 in virologically suppressed subjects with HIV-1 infection after analytical treatment interruption. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 22, 2021. NLM Identifier: NCT04819347. Accessed February 26, 2024
14. Frontier Biotechnologies Inc. A multicenter, two-arm, 24-week study of albuvirtide in combination with 3BNC117 in patients with multi-drug resistant (MDR) HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 17, 2020. NLM Identifier: NCT04560569. Accessed February 26, 2024
15. Chinese Clinical Trial Registry. ChiCTR number: ChiCTR2100053311; Study on albuvirtide intensification of antiretroviral therapy in HIV infected patients with poor immune restoration. Accessed February 26, 2024
16. Ma P, Gao L, Zhang D, Huang R, Yu A, Xia H. Effects of albuvirtide intensification on CD4 T cell reconstitution in acquiring HIV clients with incomplete immune reconstitution. Abstract presented at: European AIDS Conference; October 18-21, 2023; Warsaw, Poland. Abstract eP.A.035. Accessed February 26, 2024
17. Wu H, Yao C, Zhang T, et al. Efficacy and safety of long acting HIV fusion inhibitor albuvirtide in treatment-experienced HIV-1 infected patients: week 48 analysis from the randomized controlled phase 3 TALENT study. Abstract presented at: IAS Conference on HIV Science; July 18-21, 2021; Virtual. Abstract PEB148. Accessed February 26, 2024
18. Yang W, Xiao Q, Wang D, Yao C, Yang J. Evaluation of pharmacokinetic interactions between long-acting HIV-1 fusion inhibitor albuvirtide and lopinavir/ritonavir, in HIV-infected subjects, combined with clinical study and simulation results. Xenobiotica Fate Foreign Compd Biol Syst. 2017;47(2):133-143. Accessed February 26, 2024

Last Reviewed: February 26, 2024