Anrukinzumab, also known as IMA-638, is a humanized antibody designed to target at interleukin 13 (IL-13). This drug was developed by Wyeth with an attempt for the treatment of asthma. Up to now, anrukinzumab has been investigated in the clinical treatment for persistent asthma, allergen-induced airway response in subjects with mild atopic asthma, and ulcerative colitis. In 2015, a pharmacokinetic comparison of anrukinzumab was conducted among healthy volunteers, asthma and ulcerative colitis to identify covariates. Results showed that patients with ulcerative colitis are more likely to have a fast clearance than other two groups, so more doses level may be required. In addition, anrukinzumab's phase IIa study in active ulcerative colitis was also studied. The results showed that anrukinzumab could bind to IL-13, but the therapeutic effect of ulcerative colitis was not statistically significant. Thus, the phase II study for ulcerative colitis was discontinued in countries including Austria, Bulgaria, and Canada.
Interleukin 13 (IL-13), the target molecular of anrukinzumab, is a cytokine of chemokine family. IL-13 is a cytokine with multiple immunomodulatory functions, which is mainly secreted by Th2 cells. IL-13 receptors are widely distributed, including B cells, monocytes, macrophages, basophils, mast cells and so on. When IL-13 binds to its receptor complex, it can activate three intracellular signaling pathways, namely, JAK/STAT pathway, PI-3K pathway and MAPK pathway, to play a biological role. It has been found that IL-13 can participate in the maintenance of asthma inflammation by inducing eosinophil infiltration and promoting IgE secretion. In addition, IL-13 can also induce airway hyper reactivity (AHR) and small airway structural remodeling, which plays an important role in the pathogenesis of asthma. Therefore, it is regarded as an ideal target for asthma treatment. The application of IL-13 antagonist to block the biological activity of IL-13 has become a good strategy to improve the persistent state of asthma. Anrukinzumab is one of many antagonists that treat ulcers and asthma by acting on IL-13.
Fig.1 Mechanism of Action of Anrukinzumab