Drugs

Albuvirtide

Other Names: ABT, Aikening, FB006M Drug Class: Fusion Inhibitor Registry Number: 1417179-66-8 (CAS) Organization: Frontier Biotechnologies Co., Ltd Phase of Development: Albuvirtide is in Phase 3 development for HIV treatment. In June 2018, albuvirtide received marketing approval in China for the treatment of HIV.

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 and Treatment Action Group Pipeline Report 20193)

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

Half-life (T½): 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.7

Resistance: The TALENT study is a Phase 3 trial (NCT02369965) evaluating albuvirtide plus lopinavir/ritonavir versus lopinavir/ritonavir plus two NRTIs in treatment-experienced participants. An interim analysis at Week 48 found that among five participants receiving albuvirtide who had HIV RNA levels at or above 400 copies/mL at Weeks 24 or 48, no treatment-emergent mutations were detected in gp41. Resistance to lopinavir/ritonavir developed in one participant in each of the treatment groups.8


Select Clinical Trials


Study Identifiers: 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:

Study Identifiers: TALENT; NCT02369965
Sponsor: Frontier Biotechnologies Inc.
Phase: 3
Status: The recruitment status of this study is unknown.
Study Purpose: The purpose of this 48-week open-label trial is to determine the safety and efficacy of albuvirtide plus lopinavir/ritonavir.
Study Population:

  • Participants are children and adults (age 16 to 60 years) with HIV and who have had treatment failure while on a standard first-line ART regimen. Participants have received previous ART with NRTIs/NNRTIs for more than 6 months.
  • Participants have HIV RNA ≥1,000 copies/mL.9
Selected Study Results:
Study Identifiers: NCT03719664
Sponsor: Frontier Biotechnologies Inc.
Phase: 2
Status: This study is currently recruiting participants.
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 copies/mm3 at screening.10


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, 389 participants who had experienced first-line ARV treatment failure were randomized to either albuvirtide plus lopinavir/ritonavir or lopinavir/ritonavir plus two NRTIs. An interim analysis was performed on data from 208 participants; the safety analysis subset included 192 treated participants (n = 93 albuvirtide group; n = 99 NRTI group). SAEs occurred in 5.6% of participants in the albuvirtide group versus 3.0% of participants in the NRTI group. Only one SAE, which occurred in the NRTI group, was drug-related. The two groups had similar AE rates. The most common drug-related AEs observed in the albuvirtide-treated participants, all mild to moderate in intensity, were diarrhea (7.5%), headache (2.2%), and dizziness (2.2%).8

The most common drug-related laboratory abnormalities in the albuvirtide group were high cholesterol and high triglycerides, with the majority of these cases being mild to moderate in intensity. High cholesterol was noted to occur more frequently in the albuvirtide group (12.9%) than in the NRTI group (2.0%). No injection site reactions were observed. Albuvirtide did not affect serum creatinine or eGFR levels.8


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.11


References


  1. United States National Library of Medicine. ChemIDplus Advanced: Albuvirtide. https://chem.nlm.nih.gov/chemidplus/rn/1417179-66-8. Accessed July 31, 2019
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed July 31, 2019
  3. Jefferys R. Antiretroviral Therapy Pipeline 2019. Treatment Action Group Pipeline Report 2019. http://www.treatmentactiongroup.org/sites/default/files/pipeline_arv_therapy_2019.pdf. Accessed July 31, 2019
  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). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3293837/. Accessed July 31, 2019
  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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748529/. Accessed July 31, 2019
  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.
  7. 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. http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=e1c18d5b-830f-4b4e-8671-35bcfb20eed5&cKey=70d14bcc-bad6-4754-b4b1-66b7d2559a23&mKey=%7b6B114A1D-85A4-4054-A83B-04D8B9B8749F%7d. Accessed July 31, 2019
  8. Xie D. Efficacy and safety of long acting HIV fusion inhibitor albuvirtide in antiretroviral-experienced adults with HIV-1: Interim 48 week results from the randomized, controlled, Phase 3, non-inferiority TALENT study. Webcast presented at: International Congress of Drug Therapy in HIV Infection (HIV Glasgow); October 23-26, 2016; Glasgow, United Kingdom. https://vimeo.com/189136480. Accessed July 31, 2019
  9. Frontier Biotechnologies Inc. Efficacy and safety of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults failed standard first-line ART regimen. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 18, 2015. NLM Identifier: NCT02369965. https://clinicaltrials.gov/ct2/show/NCT02369965. Accessed July 31, 2019
  10. 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. https://clinicaltrials.gov/ct2/show/NCT03719664. Accessed July 31, 2019
  11. 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.


Last Reviewed: July 31, 2019