This paper outlines the mechanisms of complement activation. CCX168 has garnered attention as a potential replacement for corticosteroids, so CCX168 holds promise.
#IS ATC4 A VIRUS TRIAL#
In a phase II clinical trial of CCX168 to treat anti-neutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis (AARV), administration of CCX168 (+cyclophosphamide) was as efficacious as or more efficacious than the standard treatment (high-dose prednisolone + cyclophosphamide). CCX168 is an orally administered C5a receptor antagonist.
CCX168 was recently developed to inhibit inflammation caused by C5a. Eculizumab binds to C5 and thus inhibits the cleavage of C5 into C5a and C5b, but its principal action is presumably by inhibiting the formation of C5b, which precludes the formation of MAC. Over the past few years, a monoclonal antibody against complement component C5 (eculizumab) has been approved as a treatment for paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome (aHUS), and this antibody has yielded encouraging results. Complement fragments such as C3a, C4a, and C5a trigger inflammation as anaphylatoxins and chemotactic factors, and abnormal complement activation leads to various inflammatory diseases. Complement activation results in the formation of membrane attack complex (MAC), and this complex produces holes in the cell membrane, causing the destruction of target cells. These proteins are activated sequential order in a cascade that produces a variety of molecules that maintain homeostasis in the body by, for example, defending the body from infection.
The complement system consists of more than 30 proteins.