Leronlimab is being investigated as a potential HIV-PrEP drug in an early human clinical trial

An experimental, laboratory-made antibody can completely prevent non-human primates from infecting the monkey form of HIV, new research published in Nature Communications shows.

The results will feed into a future human clinical trial investigating leronlimab as a potential pre-exposure prophylaxis or PrEP therapy to prevent infection in humans with the AIDS-causing virus.

“Our study results suggest that leronlimab may be a new weapon against the HIV epidemic,” said the study’s lead researcher and co-author, Jonah Sacha, Ph.D., professor at Oregon Health & Science University at Oregon National. the OHSU Primate Center and Institute for Vaccines and Gene Therapy.

“The results of this preclinical study targeting the HIV co-receptor CCR5 have the potential to be groundbreaking as we essentially have a tool that can mimic the genetic mutations in CCR5 that make some individuals immune to infection make and partially cure HIV, “said the other corresponding author, Lishomwa Ndhlovu, MD, Ph.D., professor of immunology in medicine at Weill Cornell Medicine in New York.

The monoclonal antibody, made by CytoDyn of Vancouver, Washington, blocks the entry of HIV into immune cells through a surface protein called CCR5. The injectable drug has already been investigated in a Phase 3 study as a potential treatment for people with HIV when used in combination with standard antiretroviral drugs. CytoDyn is in the process of submitting information to the FDA to apply for approval for this use. In this study, however, the prevention of HIV infection was initially examined specifically.

Some PrEP drugs are already available, but they can cause undesirable side effects such as liver, heart, and bone problems, and some people are resistant to them because of genetic mutations in HIV. Existing PrEP options usually require frequent use, such as a daily pill, or are IV fluids to be given in a clinic. Leronlimab is designed as an injection for self-administration.

To study the effectiveness of leronlimab as a potential PrEP drug, the research team at the OHSU’s Oregon National Primate Research Center created three groups of six rhesus monkeys. Two groups received different doses of leronlimab while the third served as a control that did not receive the experimental drug.

Macaques, which received the higher dose of 50 milligrams per kilogram of animal weight every other week, were completely protected from the monkey form of HIV. In contrast, two of the animals that received the lower dose of 10 milligrams per kilogram per week became infected and each animal in the control group became infected. The researchers concluded that the low-dose group’s partial protection was likely due to the monkey’s immune response to the human antibody.

Based on the results of this study, CytoDyn plans to conduct an early clinical trial within the next year evaluating leronlimab as a potential PrEP drug in humans. Human doses would likely be lower than those reported in this study because Rhesus macaque cells have more CCR5 surface protein than humans.

In the meantime, Sacha is already trying to make Leronlimab easier to use. In August 2020, he received a five-year NIH grant of $ 3 million to develop a concentrated, longer-lasting formulation of leronlimab that could allow it to be injected every three months. Less frequent injections can increase the adherence of the drug and thus improve the effectiveness of the drug.

The research team dedicated this study to Timothy Ray Brown, who died on September 29, 2020 and was known as a Berlin patient who became the first person to be cured of HIV. While living in Berlin in 2007, Brown underwent a morning bone transplant to treat his blood cancer. The procedure eliminated HIV in Brown because the transplanted bone marrow was from a donor who had a rare mutation that eliminated the CCR5 gene, which makes the surface protein that makes HIV enter cells. Sacha befriended Brown after meeting him at an AIDS conference in 2015. Brown is also the co-author of the paper and inspired scientists who worked on this research.

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