Pre‐ and Postnatal Development Study of Nemolizumab, a Humanized Anti‐Interleukin‐31 Receptor A Monoclonal Antibody, in Cynomolgus Monkey

ABSTRACT Background Nemolizumab, a humanized monoclonal antibody against interleukin‐31 receptor A (IL‐31RA), is used to treat atopic dermatitis and prurigo nodularis. These inflammatory skin diseases affect a wide range of age groups, including pregnant women and children; however, little is known about their biological effects on pre‐ and postnatal development. Therefore, we report and discuss the results of an enhanced pre‐ and postnatal development study in cynomolgus monkeys treated with nemolizumab, which also incorporates an assessment of juvenile toxicities. Methods Nemolizumab was subcutaneously administered at doses of 1 or 25 mg/kg to pregnant cynomolgus monkeys once every 2 weeks (biweekly) from Gestation Day 20 until delivery, to investigate the potential toxicities on pre‐ and postnatal development. Additionally, their offspring were subcutaneously dosed biweekly with 1 or 25 mg/kg from approximately 1 to 7 months after birth to investigate the potential toxicities on juveniles, considering the age of the target patient population. The examination included tests for immune function and nervous system involvement by IL‐31, as well as the standard assessments outlined in the ICH S5 guideline to comprehensively assess the safety profile. Results No nemolizumab‐related toxicities were observed in both dams and offspring up to 25 mg/kg. Maternal plasma nemolizumab concentrations were well maintained during the gestation period, gradually decreasing after delivery. Plasma concentrations in the offspring, higher than in dams, was maintained until scheduled necropsy. Conclusion Blocking IL‐31 signaling with repeated dosing of nemolizumab did not adversely affect pregnancy, parturition, nursing, or postnatal physical and functional development in cynomolgus monkeys.