Monoclonal antibody demonstrates ‘unprecedented’ virologic suppression in HIV study
The monoclonal antibody UB-421 “demonstrated unprecedented and sustained” virologic suppression in the absence of ART among people with HIV during a nonrandomized, open-label, phase 2 clinical study, according to findings published today by The New England Journal of Medicine.
UB-421 blocks the virus-binding site on CD4+ cells, Chang-Yi Wang, PhD, cofounder and chief scientific officer for United Biomedical — which is developing the treatment — and colleagues explained.
In their study, Wang and colleagues gave participants eight IV infusions of UB-421 following analytic treatment interruption (ATI) of their ART regimen.
“As we all know, an HIV diagnosis is not the death sentence it once was. Current treatments require a daily cocktail of ART drugs to keep the infection in check,” Wang told Infectious Disease News. “To minimize the spread of HIV, patients are required to take a combo regimen selected from six different classes of HIV drugs. Therefore, the patients’ greatest struggle is contending with the daily regimen of pills, unappreciated long-term toxicity and stigma. These can impact a patient’s quality of life.”
Wang said there are several benefits to antibody drugs.
“One, antibodies have long half-lives and can be administered with less a frequent dosing schedule, such as ... weekly, semi-monthly or even monthly,” Wang said. “Two, biological protein drugs have lower toxicities to the liver, kidneys, etc. And three, certain antibody drugs, such as UB-421, can exhibit beneficial immunomodulatory effects that cannot be achieved by small molecule drugs.”
Last year, researchers at the National Institute of Allergy and Infectious Diseases found that short-term ATI did not increase the HIV reservoir size or cause irreversible damage to the immune system, supporting its use to determine the efficacy of ART-free novel therapeutics on virologic suppression.
The UB-421 study enrolled 29 HIV-infected adults in Taiwan, all with undetectable viral loads (less than 20 copies/mL) at screening, and separated them into two cohorts. The first cohort included 14 participants who received a dose of 10 mg/kg of body weight every week for 8 weeks, whereas the 15 participants in the second cohort received a dose of 25 mg/kg of body weight every 2 weeks for 16 weeks. The primary outcome was time to viral rebound.
According to the study findings, all patients in both cohorts maintained virologic suppression during ATI. Wang and colleagues observed what they called “intermittent viral blips” in 28% of participants, although these “did not result in additional treatment.” No participants had a viral rebound more than 400 copies/mL, CD4+ counts remained stable and there was a decrease in CD4+ regulatory T cells during UB-421 monotherapy, they reported.
The most common adverse event was rash, with 52% of all participants experiencing a mild transitory rash. Some 41% reported a grade 1 rash and 10% reported a grade 2 rash, which contributed to one participant discontinuing the study.
“When UB-421 was used as a monotherapy, our antibody reduced the levels of plasma HIV RNA to undetectable levels in a patient's system, the same low levels as antiretroviral treatment,” Wang said. “Over the 2- to 4-month course of treatment, the disease was suppressed in all patients with no generation of treatment-resistant mutated HIV. We have demonstrated unprecedented and sustained suppression of the virus in all patients and achieved a 100% success rate in this study.” – by Marley Ghizzone
Disclosures: Wang is employed by United Biomedical and reports having several U.S. patents pending for antibodies against HIV, issued or licensed. Please see the study for all other authors’ relevant financial disclosures.