HGS004

HGS004 is a human immunoglobulin (Ig) G4 monoclonal antibody against CCR5 that is being developed by Quest Clinical Research. HGS004 binds to and inhibits the activity of the CCR5 receptor on the cell surface. HIV uses both the CCR5 and the CD4 receptors to gain entry to the cell, but CCR5 is the primary receptor enabling HIV transmission and replication from the early stages of infection through to progression to AIDS.

Small-molecule CCR5 inhibitors like maraviroc and vicriviroc have been shown to be effective HIV treatments, leading to maraviroc gaining a license last year.

The advantages of monoclonal antibody drugs to traditional small-molecule drugs is that they can be dosed less frequently, biweekly or even monthly; they usually do not interfere with other drugs (allowing greater freedom in choosing an optimised treatment therapy); and they should also work, at least theoretically, against resistant viral strains. The formulation of HGS004 is as an injectable drug.

Preclinical research with HGS004 has shown that it binds tightly to human CCR5, preventing HIV entry and viral transmission.

An early dose-ranging study of HGS004 in over sixty patients infected with CCR5-tropic HIV found the drug to be safe, well tolerated, and effective. A tenfold reduction in viral load was seen in 54% of the study participants.¹

Investigators involved in this study suggest further studies should be carried out with HGS101. This is a derivative of HGS004 that shares the same characteristics, but has five to ten times the potency of the original drug.