Afasevikumab, also known as RG7624, is a human antibody inhibitor for human interleukin 17A (IL17A) and interleukin 17F (IL17F). This drug was developed by Genentech and has been investigated in the study of the treatment of inflammation diseases like autoimmune disorders. In 2013, Genentech completed a phase Ib study for the treatment of autoimmune disorders in Canada. However, it had been discontinued in 2015. In 2016, researchers used afasevikumab to conduct a phase I clinical trials for the treatment of inflammation in USA with no specified.
Afasevikumab is an IgG1κ type anti-inflammatory through interacting with cytokine IL-17A and IL-17F. Both IL-17A and IL-17F belong to IL-17 family, and are a kind of inflammatory cytokine. IL-17A is produced by activated T cells, which can regulate the activity of NF-κB and mitogen-activated protein kinase and stimulate the expression of IL6 and cyclooxygenase-2 (PTGS2 / COX-2). It has been found that IL-17A promotes the occurrence of a variety of inflammatory diseases by promoting the expression of cytokines and chemokines in a variety of cells. The role of IL-17A in autoimmune diseases such as multiple sclerosis, rheumatic arthritis, inflammatory enteritis, psoriasis and so on has been reported. At the same time, IL-17A can also resist the invasion of exogenous pathogens by inducing the expression of cytokines and antibacterial peptides. IL-17F and IL-17A have the highest homology, and their cell origin and effect are also the most similar. Studies have found that IL-17F plays a pro-inflammatory role in allergic diseases such as asthma, and that IL-17F can up-regulate and participate in the anti-infection effect of the lung by recruiting and activating neutrophils. In the mouse model of acute respiratory tract mycoplasma infection, IL-17F can induce HaCaT cell line to produce IL-8, involved in the pathogenesis of psoriasis. Therefore, targeting IL-17A and IL-17F has become a new strategy for the treatment of inflammatory diseases. Afasevikumab is one of the monoclonal antibodies that inhibit IL-17A and IL-17F.
Fig.1 Mechanism of Action of Afasevikumab