The findings also highlight additional mechanistic, drug product stability, pharmacokinetics and toxicology studies that support the candidate as a potential HIV prevention and treatment.
Preclinical data published by Nature Communications show an investigational ultra-long-acting antiretroviral from Exavir Therapeutics lead to year-long plasma drug levels deemed sufficient for the treatment and prevention of HIV, at least in animal models.
The preclinical research findings also highlight additional mechanistic, drug product stability, pharmacokinetics and toxicology studies that support the candidate as a potential best-in-class, once-annual antiretroviral injectable agent in the setting of HIV prevention and treatment.
“These results demonstrate the two-part mechanism that enables the apparent ultra-long half-life of XVIR-110, as well as the rigor and reproducibility of our broader findings,” according to a statement made by Benson Edagwa, the scientific co-founder of Exavir Therapeutics and Associate Professor at the University of Nebraska Medical Center. “Our agent is room-temperature stable, has been well tolerated in animal studies, and can provide effective drug concentrations for over a year with a single injection.”
In the most recent Nature publication, researchers showed that a single injection of Exavir’s proprietary nanocrystal NM2CAB formulation led to therapeutic exposures of the cabotegravir stearoylate prodrug to monkeys, mice and rates for more than a year.
According to the company, the mechanism of the apparent ultra-long half-life of XVIR-110 was predominantly associated with lipophilic nanocrystal dissolution. In preliminary toxicology studies, XVIR-110 has been shown to be well tolerated at all studied dose levels in all tested species.
HIV is a viral infection associated with one of the highest mortality rates. Current estimates place HIV infection in approximately 1.2 million people in the United States alone. Each year, up to $30 billion is spent on antiretroviral HIV therapies across the globe.
The U.S. Food and Drug Administration recently approved a once-monthly, long-acting injectable formulation of cabotegravir in combination with long-acting injectable rilpivirine in the setting of HIV treatment.
Recent Phase III trials have also shown that an investigational, once every eight-week long-acting injectable formulation of cabotegravir is superior to standard of care for pre-exposure prophylaxis.
Dr. Howard Gendelman, scientific co-founder of Exavir Therapeutics and Professor of Medicine at the University of Nebraska Medical Center, noted in a statement on XVIR-110 that today’s HIV treatment and prevention paradigm currently consists of daily oral agents that may increase the risk of viral resistance, in addition to psychological burden for patients with HIV or who are at risk of HIV.
“There has been a resounding shift towards long-acting antiretrovirals in the HIV community,” explained Dr. Gendelman. “Although progress has been made in recent years, there continues to be a significant unmet need for injectable antiretrovirals with longer durations and combination partners for the existing long-acting antiretroviral armamentarium.”
In addition to Exavir’s work in HIV, other companies are also on the quest to discover an effective treatment and prevention agent for the viral infection. Texas-based Enzolytics, for instance, has patented its ITV-1 therapeutic for HIV treatment. This therapeutic is a suspension comprising Inactivated Pepsin Fraction (IPF), which in previous studies has been shown to be an effective treatment for HIV/AIDS. Additionally, other studies have shown ITV-1 to significantly modulate the immune system, suggesting the agent may have therapeutic potential in HIV and possibly other viral infections.
