Taiwan-headquartered United BioPharma (UBP) says the U.S. Food and Drug Administration (FDA) has approved a phase 2 clinical trial IND submitted by the U.S. National Institute of Allergy and Infectious Diseases (NIAID) of NIH.
The purpose of the study is to assess the safety and antiviral activity of UB-421 in combination with optimized background ART in HIV-1 infected patients with multi-drug resistance (MDR).
The study protocol is entitled: “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 the NIAID/NIH-sponsored trial, UBP will be responsible for supplying the investigational drug, UB-421.
About the United BioPharma and NIAID partnership
United BioPharma has been collaborating with NIAID since 2015 to study the properties of UB-421 for treatment of HIV. The efficacy of UB-421 against HIV clinical isolates resistant to HIV broadly neutralizing antibodies, entry inhibitors, and other antiretroviral drugs is well documented, the company said.
“We are excited for the NIAID to recognize the effectiveness of UB-421 through extensive collaborative studies, and to sponsor a phase 2 clinical trial in multi-drug resistant HIV patients.” said Shugene Lynn, CEO and president of United BioPharma.
The treatment of HIV-1 infection with antiretroviral therapy (ART) has significantly decreased HIV-1-related mortality and transformed HIV-1 infection into a treatable chronic disease. Successive generations of ART agents have shown improved efficacy and tolerability while minimizing drug-related toxicities.
However, the ability of HIV-1 to develop resistance to multiple classes of antiretroviral (ARV) drugs continues to present challenges to the treatment of some ARV treatment-experienced patients.
MDR HIV-1 has been associated with a higher risk of disease progression and death. Therefore, new agents and drug classes are necessary to keep up with ongoing viral mutations in an attempt to achieve sustained suppression of HIV-1 plasma viremia, and to prolong the life of those with MDR HIV infection, as well as to prevent viral replication and transmission of such MDR strains. Drugs with novel mechanism of action, such as UB-421, are of particular interest because empirical resistance is unlikely.
UB-421 is an Fc-aglycosylated, non-T cell depleting and CD4-specific humanized IgG1 derived from the parent murine B4, which binds to discontinuous, conformational epitopes on the HIV-receptor complex, including CD4 (domain 1), and competitively blocks HIV entry.
Both the murine and humanized mAbs bind to CD4+ T cells with approximately 50-100-fold higher affinity than HIV-gp120. UB-421 has been shown to inhibit viral entry with viral load reduction potency in phase 1 and phase 2a clinical studies involving treatment-naïve HIV-infected patients.
In the phase 2 study with ART-stabilized HIV-infected patients, UB-421 monotherapy maintained viral suppression for up to 16 weeks without viral rebound in the absence of ART. UB-421 is currently in the stage of phase 2 and phase 3 clinical trials for ART substitution, treatment of multi-drug resistant HIV as well as proof-of-concept study of HIV functional cure.