ABX464 — a first-in-class small molecule that blocks HIV replication — significantly reduced viral reservoir 28 days after treatment, according to findings from a phase 2a study presented at the 8th International Workshop on HIV Persistence during Therapy.
“These data from the ABX464-005 study are very exciting and suggest that ABX464 could potentially play a critical role in future HIV eradication or cure strategies,” Ross Cranston, MD, FRCP, principal investigator at Germans Trias i Pujol University Hospital Badalona in Barcelona, said in a press release.
In previous clinical studies, ABX464 was associated with a dose-dependent reduction in HIV RNA in treatment-naive study participants, and the treatment decreased HIV-1 DNA in peripheral blood mononuclear cells (PBMC) in virally suppressed patients, according to the release. ABX464 is being developed by the biotechnology company Abivax.
For the current study, Cranston and colleagues evaluated the safety, pharmacokinetic (PK) and pharmacodynamic (PD) profile of ABX464 in 11 men with a CD4 nadir of at least 250 cells/mm3 and plasma HIV-1 RNA of 100,000 copies/mL or less. The participants received 150 mg of oral ABX464 for 28 days. Reductions in the HIV reservoir were assessed with digital droplet PCR in blood and rectal biopsy samples that were collected at baseline and days 28 and 56.
Overall, CD4 T cells with HIV-1 DNA decreased from 191.1 (interquartile range, 80.1-368.1) to 116 (IQR, 97.4-1185) copies between baseline and day 28 (P = .01). However, no further significant reductions were observed between days 28 and 56.
Two participants discontinued treatment because of adverse events, which included abdominal pain, headache, hyperamylasemia, hyperlipasemia, myalgia, asthenia, insomnia and backache, but no serious adverse events were reported.
According to Jean-Marc Steens, MD, chief medical officer of Abivax, ABX464 appears to have a favorable safety profile compared with currently available ART, which can cause nausea, diarrhea, fatigue, elevated liver function tests, new or worsening of kidney disease, decreases in bone density, effects on the nervous system, abnormal fat distribution and insulin resistance.
Steens told Infectious Disease News that the company’s next steps will be to generate data on ABX464’s ability to reduce HIV reservoir in the gut lymphoid tissue.
“Our hope is that ABX464 will demonstrate the potential to reduce or eliminate the viral reservoir in these tissues of the body, the cells of which are closely associated with viral rebound,” he said.
If, down the line, ABX464 were to be approved for use, Steens said it would offer patients with HIV “a therapy with a novel mechanism of action that improves outcomes better than currently available treatments.”
“ABX464 has demonstrated a potential for long-lasting activity interruption of treatment. Two independent clinical studies have now confirmed its potential to reduce the HIV reservoir after 28 days of administration of ABX464,” he said. “This would represent a potential functional cure for HIV, and would allow patients, who currently take medications every day of their lives to keep the virus in check to take medication less frequently.” – by Stephanie Viguers
Steens JM, et al. Abstract #00023. Presented at: 8th International Workshop on HIV Persistence during Therapy; Nov.12-15, 2017; Miami.
Disclosure: Steens is an employee of Abivax. Infectious Disease News was unable to confirm relevant financial disclosures for Cranston at the time of publication.