Date: 2016-02-24
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the 2016 Conference on Retroviruses and Opportunistic Infections (CROI) in Boston
Company: Gilead Sciences (USA - CA)
Product: GS-9620 and GS-986
Action
mechanism: Toll-like receptor 7 agonist/TLR7 agonist
Disease: HIV eradication strategy
Therapeutic area: Infectious diseases
Country:
Trial details:
Latest
news: * On February 24, 2016, Gilead Sciences announced results from a preclinical study conducted in collaboration with researchers at Beth Israel Deaconess Medical Center evaluating a proprietary investigational oral toll-like receptor 7 (TLR7) agonist, GS-9620, and a related molecular analogue, GS-986, as part of an HIV eradication strategy. Data from the study conducted in simian immunodeficiency virus (SIV)-infected virally suppressed rhesus macaques on antiretroviral therapy (ART) demonstrate that TLR7 agonist treatment induced transient plasma SIV RNA blips and reduced SIV DNA. In addition, TLR7 agonist treatment resulted in subsequent prolonged virus suppression in some of the macaques after stopping ART. These data were presented in an oral session (Session O-7) at the 2016 Conference on Retroviruses and Opportunistic Infections (CROI) in Boston. Earlier research presented at CROI 2015 showed that GS-986 treatment, in combination with ART, reduced SIV DNA levels by 30 to 90 percent in some tissues. This follow-up study was designed to assess whether GS-9620 produced results similar to GS-986, and whether lower doses of the compounds would induce transient plasma viremia and/or perturb SIV viral reservoirs. A lower dose was chosen with the intent to minimize induction of peripheral interferon-alpha (IFN-alpha), an anti-viral protein that can cause adverse events. In this placebo-controlled study, SIV-infected rhesus macaques received ART beginning day 65 post-infection. All animals achieved and maintained viral suppression (plasma RNA less than 50 copies/mL) through week 67 when they received 10 to 19 doses of either GS-9620 or GS-986 every other week. TLR7 agonist dosing induced transient and variable increases in plasma SIV RNA levels across all treatment groups. After completing all doses of TLR7 agonist and prior to stopping ART, peripheral lymphocytes and lymph node biopsies from the animals had less inducible virus. Two of the TLR7 agonist-treated rhesus macaques maintained undetectable plasma viral load for more than 90 days after stopping ART. Gilead Sciences has now advanced research on GS-9620 to a Phase 1b safety study in HIV-infected individuals taking ART.
