Drug information

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Semzuvolimab
Other Names
UB-421, mAb dB4, mAb dB4C7
Drug Class
CD4 Attachment Inhibitor
Registry Number
2409099-32-5 (CAS)
Organization
United BioPharma
Phase of Development

Semzuvolimab is in Phase 3 development for HIV treatment.

(Compound details obtained from PubChem,1 ClinicalTrials.gov,2 and Treatment Action Group Pipeline Report 20233) 

Pharmacology

Pharmacology

Mechanism of Action

CD4 attachment inhibitor. Semzuvolimab is a humanized IgG1 monoclonal antibody (mAb) that is aglycosylated at the Fc region. Semzuvolimab competitively binds to domain 1 of CD4 receptors and inhibits HIV-1 attachment to and entry into cells. In vitro, semzuvolimab 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 semzuvolimab 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 semzuvolimab did not develop in any participants.6

Select Clinical Trials

Select Clinical Trials

Study Identifiers: Protocol A201-HIV; 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 semzuvolimab monotherapy in treatment-naive adults. Semzuvolimab'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 Identifiers: UBP-A202-HIV; 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 semzuvolimab 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: Results published in the New England Journal of Medicine (2019) showed that treatment with semzuvolimab was safe and effective. All participants maintained viral suppression while receiving semzuvolimab monotherapy during an analytical treatment interruption of ART (lasting 8 or 16 weeks).6

Study Identifiers: UBP-A209-HIV; NCT03743376

Sponsor: United BioPharma
Phase: 2
Status: This study has been completed.
Study Purpose: The purpose of this open-label trial was to evaluate the safety of semzuvolimab and its efficacy in reducing the HIV reservoir when used in conjunction with ART.
Study Population: Participants were adults with HIV who had HIV RNA <50 copies/mL.9

Study Identifiers: UBP-A205-HIV; 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 semzuvolimab 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 Identifiers: UBP-A230-HIV; 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 semzuvolimab plus the latency-reversing agent tucidinostat and the ability of this regimen in reducing the HIV reservoir in participants undergoing an analytical 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 had HIV RNA <50 copies/mL for at least 12 months prior to screening.
  • Participants have had CD4 counts ≥200 cells/mm3 within the 12 weeks prior to screening.11

Study Identifiers: UBP-A218-HIV; 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 semzuvolimab and its efficacy in reducing the HIV reservoir when used in combination with ART.
Study Population: Participants are adults with HIV who are receiving ART and have HIV RNA <50 copies/mL at screening.12

Study Identifiers: UBP-A232-HIV; NCT05056974

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 of semzuvolimab monotherapy plus the latency-reversing agent tucidinostat and the ability of this regimen in changing the latent HIV reservoir in participants undergoing an analytical treatment interruption of ART.
Study Population:

  • Participants were adults with HIV who had been receiving ART for more than 3 years prior to screening.
  • Participants had stable viral suppression.13

Study Identifier: NCT05582694

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Phase: 2
Status: This study is currently recruiting participants.
Study Purpose: The purpose of this open-label study is to evaluate the efficacy of semzuvolimab 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 receiving ART for at least 6 months. Participants have been receiving a failing ART regimen for at least 8 weeks prior to screening or have experienced treatment failure within 8 weeks of screening and are off ART.
  • Participants have HIV RNA ≥1,000 copies/mL and CD4 counts >350 cells/mm3 at screening.
  • Participants have viral sensitivity to at least one approved ARV agent.14

Study Identifiers: UBP-A308-HIV; 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 semzuvolimab 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.2

Additional studies evaluating semzuvolimab for HIV treatment have been or are being conducted, including the following early-phase trials:

  • UBP-A122-HIV (NCT04620304): A Phase 1, open-label, dose-escalation study to evaluate the safety, pharmacokinetics, and antiviral activity of a subcutaneous (SC) formulation of semzuvolimab in treatment-naive adults with HIV. This study has been completed.15
  • UBP-A127-HIV (NCT04620291): A Phase 1 study to evaluate the safety, pharmacokinetics and antiviral activity of a SC formulation of semzuvolimab in treatment-experienced adults with HIV who are aviremic in addition to treatment-naive adults with HIV. See the ClinicalTrials.gov record for this study’s status.16

Adverse Events

Adverse Events

UBP-A202-HIV (NCT02369146)

In this Phase 2 study of semzuvolimab in 29 treatment-experienced adults, the most common adverse event (AE) that was possibly or probably related to semzuvolimab 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 study. One participant discontinued semzuvolimab 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 semzuvolimab are currently unknown.

References

References

  1. National Center for Biotechnology Information. PubChem substance record for SID 472420724, semzuvolimab, Source: FDA Global Substance Registration System (GSRS). Accessed October 3, 2023
  2. 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. Accessed October 3, 2023
  3. Jefferys R. The antiretroviral therapy pipeline 2023. Treatment Action Group Pipeline Report 2023. Accessed October 3, 2023
  4. United BioPharma website. Pipeline. Accessed October 3, 2023
  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. Accessed October 3, 2023
  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. Accessed October 3, 2023
  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. Accessed October 3, 2023
  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. Accessed October 3, 2023
  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. Accessed October 3, 2023
  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. Accessed October 3, 2023
  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. Accessed October 3, 2023
  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. Accessed October 3, 2023
  13. United BioPharma. A Phase II proof-of-concept trial to evaluate the safety and efficacy of UB-421 plus chidamide in changing HIV reservoirs among ART stabilized HIV-1 patients who undergo ART interruption. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 18, 2021. NLM Identifier: NCT05056974. Accessed October 3, 2023
  14. National Institute of Allergy and Infectious Diseases (NIAID). A single arm open label Phase 2 trial of anti-CD4 antibody UB-421 in combination with optimized background antiretroviral therapy in patients with multi-drug resistant HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 14, 2022. NLM Identifier: NCT05582694. Accessed October 3, 2023
  15. United BioPharma. A Phase I, open-label, multi-dose study for evaluation of the safety, pharmacokinetics, and antiviral activity of UB-421 subcutaneous formulation administered in HIV-1 infected treatment naive patients. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 22, 2020. NLM Identifier: NCT04620304. Accessed October 3, 2023
  16. United BioPharma. A Phase I, open-label, multi-dose study for evaluation of the safety, pharmacokinetics, and antiviral activity of UB-421 subcutaneous formulation in HIV infected adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 28, 2020. NLM Identifier: NCT04620291. Accessed October 3, 2023
Last Reviewed: October 3, 2023