Drug information

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Pronounce:
Other Names:
mAb dB4, mAb dB4C7
Drug Class:
CD4 Attachment Inhibitor
Registry Number:
1888475-19-1 (CAS)
Organization:
United Biomedical
Phase of Development:

UB-421 is in Phase 3 development for HIV treatment.

(Compound details obtained from ChemIDplus Advanced,1 ClinicalTrials.gov,2 and Treatment Action Group Pipeline Report 20213

Pharmacology

Pharmacology

Mechanism of Action: CD4 attachment inhibitor. UB-421 is a humanized IgG1 monoclonal antibody (mAb) that is aglycosolated at the Fc region. UB-421 competitively binds to domain 1 of CD4 receptors and inhibits HIV-1 attachment to and entry into cells. In vitro, UB-421 has demonstrated ability to inhibit various HIV strains, including both CXCR4- and CCR5-tropic virus.3-5

Resistance: In a small Phase 2 trial (NCT02369146) evaluating eight doses of UB-421 monotherapy (10 mg/kg every week or 25 mg/kg every 2 weeks) in 29 adults undergoing a treatment interruption of ART, drug resistance to UB-421 did not develop in any participants.6

Select Clinical Trials

Select Clinical Trials

Study Identifier: NCT01668043
Sponsor: United Biomedical
Phase: 2a
Status: This study has been completed.
Study Purpose: The purpose of this open-label trial was to evaluate two different dosages of UB-421 monotherapy in treatment-naive adults. UB-421’s safety and effectiveness in reducing viral load were assessed.
Study Population:

  • Participants were treatment-naive adults with HIV who were asymptomatic.
  • Participants had HIV RNA >5,000 copies/mL and CD4 counts >350 cells/mm3.7


Study Identifier: NCT02369146
Sponsor: United BioPharma
Phase: 2
Status: This study has been completed.
Study Purpose: The purpose of this open-label study was to evaluate the safety and effectiveness of two different dosages of UB-421 monotherapy as substitution therapy for ART.
Study Population:

  • Participants were adults with HIV who were virologically suppressed on a stable ART regimen during the past year.
  • Participants had HIV RNA <50 copies/mL and CD4 counts ≥350 cells/mm3 during the past year.5,8

Selected Study Results:


Study Identifier: NCT03743376
Sponsor: United BioPharma
Phase: 2
Status: This study is ongoing, but not recruiting participants.
Study Purpose: The purpose of this open-label trial is to evaluate the safety of UB-421 and its efficacy in reducing the HIV reservoir when used in conjunction with ART.
Study Population: Participants are adults with HIV who have HIV RNA <50 copies/mL.9


Study Identifier: NCT03164447
Sponsor: United BioPharma
Phase: 2
Status: See the ClinicalTrials.gov record for this study’s status.
Study Purpose: The purpose of this open-label study is to evaluate the efficacy, safety, and tolerability of UB-421 when used in conjunction with a failing ART regimen for 1 week and then with optimized background therapy (OBT) for 24 weeks.
Study Population:

  • Participants are adults with multidrug-resistant HIV who have been experiencing treatment failure on their current treatment regimen for at least 8 weeks prior to screening.
  • Participants have HIV RNA ≥1,000 copies/mL at screening and have had detectable viral load levels (HIV RNA >200 copies/mL) within the last 3 months before screening.
  • Participants have full viral sensitivity to at least one approved ARV agent, as determined by resistance tests at screening.10


Study Identifier: NCT04985890
Sponsor: UBP Greater China (Shanghai) Co., Ltd
Phase: 2
Status: See the ClinicalTrials.gov record for this study’s status.
Study Purpose: The purpose of this open-label study is to evaluate the safety of UB-421 plus the latency-reversing agent tucidinostat and the ability of this regimen in reducing the HIV reservoir in participants undergoing a treatment interruption of ART.
Study Population:

  • Participants are adults with HIV who have been receiving ART for more than 1 year and who have more than two different alternative optimized ART regimens available.
  • Participants have HIV RNA <50 copies/mL at screening and have had HIV RNA <50 copies/mL for at least 12 months prior to screening.
  • Participants have CD4 counts ≥350 cells/mm3 at screening and have had CD4 counts ≥350 cells/mm3 within the 12 months prior to screening.
  • Participants have total HIV DNA levels ≥300 copies per million CD4+ T cells.11


Study Identifier: NCT04404049
Sponsor: UBP Greater China (Shanghai) Co., Ltd
Phase: 2
Status: See the ClinicalTrials.gov record for this study’s status.
Study Purpose: The purpose of this open-label study is to evaluate the safety of UB-421 and its efficacy in reducing the HIV reservoir when used in combination with ART.
Study Population: Participants are adults with HIV who are virologically suppressed on ART.12


Study Identifier: NCT03149211
Sponsor: United BioPharma
Phase: 3
Status: See the ClinicalTrials.gov record for this study’s status.
Study Purpose: The purpose of this open-label study is to evaluate the safety and effectiveness of UB-421 monotherapy as substitution therapy for ART.
Study Population: Participants are adults with HIV who are virologically suppressed on a stable ART regimen.2


Study Identifier: NCT04406727
Sponsor: United BioPharma
Phase: 3
Status: See the ClinicalTrials.gov record for this study’s status.
Study Purpose: The purpose of this study is to evaluate the efficacy of UB-421 plus OBT in reducing viral load levels in participants with multidrug-resistant HIV.
Study Population: Participants are adults with multidrug-resistant HIV who have been on ART for at least 6 months and have been receiving a stable regimen for at least 8 weeks prior to screening.13

Adverse Events

Adverse Events

NCT02369146:
In this Phase 2 study of UB-421 in 29 treatment-experienced adults, the most common AE that was possibly or probably related to UB-421 was skin rash (Grade 1 or 2), occurring in 48.3% of participants. Skin rash was the only Grade 2 or higher AE that was reported during the entire study. One participant discontinued UB-421 because of rash. Grade 2 or higher laboratory abnormalities that occurred during the trial included eosinophilia and elevated liver function tests. There were no deaths or drug-related severe AEs.5,6

Drug Interactions

Drug Interactions

Drug-drug interactions associated with UB-421 are currently unknown.

References

References

  1. United States National Library of Medicine. ChemIDplus Advanced: UB-421. https://chem.nlm.nih.gov/chemidplus/rn/1888475-19-1. Accessed August 27, 2021
  2. United BioPharma. A Phase III, randomized, open-label, controlled trial to investigate the efficacy and safety of UB-421 monotherapy as substitution for stable antiretroviral therapy in HIV-1 infected adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 2, 2017. NLM Identifier: NCT03149211. https://clinicaltrials.gov/ct2/show/NCT03149211. Accessed August 27, 2021
  3. Jefferys R. The antiretroviral therapy pipeline 2021. Treatment Action Group Pipeline Report 2021. https://www.treatmentactiongroup.org/wp-content/uploads/2021/07/pipeline_2021_hiv_ARV_final.pdf. Accessed August 27, 2021
  4. United BioPharma website. Pipeline. http://www.unitedbiopharma.com/pipelines.php. Accessed August 27, 2021
  5. Wang CY, Wong WW, Tsai HC, Chen YH, Liao MJ, Lynn S. A Phase 2 Open-Label Trial of Antibody UB-421 Monotherapy as a Substitute for HAART. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 13-16, 2017; Seattle, WA. Poster 450LB. https://2jg4quetidw2blbbq2ixwziw-wpengine.netdna-ssl.com/wp-content/uploads/sites/2/posters/2017/450LB_Wong.pdf. Accessed August 27, 2021
  6. Wang CY, Wong WW, Tsai HC, et al. Effect of anti-CD4 antibody UB-421 on HIV-1 rebound after treatment interruption. N Engl J Med. 2019;380(16):1535-1545. doi:10.1056/NEJMoa1802264
  7. United Biomedical. A Phase IIa, open-label, multiple-dose trial to investigate the safety and efficacy of the UB-421 in asymptomatic HIV-1 infected adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 1, 2012. NLM Identifier: NCT01668043. https://clinicaltrials.gov/ct2/show/NCT01668043. Accessed August 27, 2021
  8. United BioPharma. A Phase II, open-label, multiple-dose trial to investigate the safety and efficacy of UB-421 monotherapy in substitution for stable antiretroviral therapy in HIV infected adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 5, 2015. NLM Identifier: NCT02369146. https://clinicaltrials.gov/ct2/show/NCT02369146. Accessed August 27, 2021
  9. United BioPharma. The HIV functional cure potential of UB-421: a Phase II, randomized, open-label, controlled, 48 week, proof of concept study, to evaluate the safety of UB-421 in combination with standard antiretroviral therapy (ART) and the efficacy of HIV reservoir reduction as compared with ART alone in ART stabilized HIV-1 patients. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 12, 2018. NLM Identifier: NCT03743376. https://clinicaltrials.gov/ct2/show/NCT03743376. Accessed August 27, 2021
  10. United BioPharma. A multicenter, single-arm, 24-week study of UB-421 in combination with optimized background therapy (OBT) regimen in patients with multi-drug resistant (MDR) HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 21, 2017. NLM Identifier: NCT03164447. https://clinicaltrials.gov/ct2/show/NCT03164447. Accessed August 27, 2021
  11. UBP Greater China (Shanghai) Co., Ltd. A proof of concept study to evaluate the safety and efficacy of UB-421 in combination with Chidamide for reduction of HIV reservoir as compared to UB-421 alone in ART stabilized HIV-1 patients who undergo ART interruption. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 8, 2021. NLM Identifier: NCT04985890. https://clinicaltrials.gov/ct2/show/NCT04985890. Accessed August 27, 2021
  12. UBP Greater China (Shanghai) Co., Ltd. The HIV functional cure potential of UB-421: a Phase II, randomized, open-label, controlled, 48 week, proof of concept study, to evaluate the safety of UB-421 in combination with standard antiretroviral therapy (ART) and the efficacy of HIV reservoir reduction as compared with ART alone in ART stabilized HIV-1 patients. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 21, 2020. NLM Identifier: NCT04404049. https://clinicaltrials.gov/ct2/show/NCT04404049. Accessed August 27, 2021
  13. United BioPharma. A randomized, double-blind, placebo-controlled Phase 3 trial with UB-421 in combination with optimized background regimen in patients with multi-drug resistant HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 22, 2020. NLM Identifier: NCT04406727. https://clinicaltrials.gov/ct2/show/NCT04406727. Accessed August 27, 2021

Last Reviewed: August 27, 2021