Drugs

UB-421

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

(Compound details obtained from ChemIDplus Advanced,1 United Biomedical, Inc. website,2 ClinicalTrials.gov,3 and Treatment Action Group HIV TB HCV Pipeline Report 20184)

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.2,4,5

In a completed Phase II study (NCT02369146), UB-421 monotherapy appeared effective as a substitution for ART in virologically suppressed adults with HIV and was shown to control viral rebound in all participants over 8 or 16 weeks of ART interruption.3  Two late-phase clinical trials are planned: One (NCT03164447) will evaluate UB-421 when used in conjunction with a failing treatment regimen for 2 weeks and then with optimized background therapy (OBT) for 24 weeks, and the other (NCT03149211) will assess UB-421 as monotherapy in suppressing viral rebound while replacing combination therapy in people with virally suppressed HIV.3,6 A Phase II trial (NCT03743376) will also be conducted to evaluate whether UB-421 used in conjunction with ART can aid in HIV reservoir reduction.7

Resistance: In a Phase IIa trial (NCT01668043) of 29 treatment-naive adults receiving UB-421 monotherapy (10 mg/kg every week or 25 mg/kg every 2 weeks), drug resistance to UB-421 did not develop in any participants.8,9


Select Clinical Trials


Study Identifiers: NCT01668043 
Sponsor: United Biomedical
Phase: IIa
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/mm3.8

Selected Study Results:


Study Identifiers
: NCT02369146 
Sponsor: United BioPharma
Phase: II
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.5,10

Selected Study Results:


Study Identifiers: NCT03743376
Sponsor:
United BioPharma
Phase:
II
Status:
See the ClinicalTrials.gov record for this study’s status.
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.7
 
Study Identifiers: NCT03164447
Sponsor: United BioPharma
Phase: II/III
Status: See the ClinicalTrials.gov record for this study’s status.
Study Purpose: The purpose of this study is to evaluate the efficacy, safety, and tolerability of UB-421 when used in conjunction with a failing treatment regimen for 2 weeks 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. 

Study Identifiers
: NCT03149211 
Sponsor: United BioPharma
Phase: III
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.3


Adverse Events


NCT01668043:
In this Phase IIa trial of UB-421 in 29 treatment-naive adults, the most common drug-related adverse events (AEs) were rash and urticaria. Two serious adverse events (SAEs)—tonsillitis and rash—were reported in one participant.8,9

NCT02369146:
In this Phase II 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.5,11


Drug Interactions


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


References


  1. United States National Library of Medicine. ChemIDplus Advanced: UB-421. https://chem.nlm.nih.gov/chemidplus/rn/1888475-19-1. Accessed May 24, 2019
  2. United Biomedical, Inc. UB-421. http://www.unitedbiomedical.com/Ub-421.htm. Accessed May 24, 2019
  3. 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 May 24, 2019
  4. Horn T. The antiretroviral pipeline. Treatment Action Group HIV TB HCV Pipeline Report 2018. http://www.pipelinereport.org/2018/hiv-antiretroviral-pipeline. Accessed May 24, 2019
  5. Wang C-Y, Wong W-W, Tsai H-C, Chen Y-H, Liao M-J, 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. http://www.croiconference.org/sites/default/files/posters-2017/450LB_Wong.pdf. Accessed May 24, 2019
  6. United BioPharma. A multicenter, randomized, parallel-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 May 24, 2019
  7. 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 May 24, 2019
  8. 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 May 24, 2019
  9. United BioPharma. Press release, dated November 26, 2014. United BioPharma completes Phase IIa clinical trial of innovative antibody drug UB-421 for AIDS treatment. http://www.unitedbiopharma.com/eng/page401_15.html. Accessed May 29, 2017
  10. 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 May 24, 2019
  11. Wang C-Y, Wong W-W, Tsai H-C, 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


Last Reviewed: May 24, 2019