Date: 2017-02-13
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the Conference on Retroviruses and Opportunistic Infections (CROI)
Company: Gilead Sciences (USA - CA)
Product: GS-CA1, HIV-1 capsid inhibitors
Action
mechanism: HIV capsid inhibitor
Disease: HIV-1 infection
Therapeutic area: Infectious diseases
Country:
Trial details:
Latest
news: * On February 13, 2017, Gilead Sciences announced findings from a preclinical study evaluating HIV capsid inhibitors (CAIs) for potential use as a long-acting antiretroviral (ARV) treatment. The study identified novel HIV-1 capsid inhibitors with highly potent antiviral activity and a favorable resistance profile to existing ARVs in vitro. The data are being presented at the 2017 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle. The preclinical study found that GS-CA1, an exemplified member of a novel class of CAIs, is a highly potent inhibitor of HIV-1 replication in human peripheral blood mononuclear cells (PBMCs) (EC50 = 140 pM) and displays similar potency against multiple HIV-1 clinical isolates from all major clades. The study also found that the identified CAIs bind to a broadly conserved site at the interface of two adjacent monomers within a capsid hexamer and accelerate capsid assembly in vitro. The identified CAIs maintained full activity in vitro against HIV-1 mutants resistant to licensed antiretrovirals (ARVs) and selected for HIV capsid variants L56I, M66I, Q67H or N74D with an attenuated in vitro replication phenotype. Preclinical mechanistic studies revealed a dual mode of action targeting both the late-stage virion maturation and post-entry capsid functions. GS-CA1 showed high in vitro metabolic stability and displayed an extended-release preclinical pharmacokinetic profile following a single subcutaneous administration that maintained target plasma concentrations for over 10 weeks. Gilead plans to evaluate a selected development candidate in Investigational New Drug (IND)-enabling toxicology studies and begin Phase 1 clinical trials in 2018.
