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

IF 1.6 4区医学 Q4 DEVELOPMENTAL BIOLOGY

Birth Defects Research Pub Date : 2025-01-27 DOI:10.1002/bdr2.2442

Ryuichi Katagiri, Saori Matsuo, Hisashi Ikegami, Akihisa Kaneko, Akihiro Arima, Shuichi Chiba, Masanori Sasaki

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引用次数: 0

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.

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人源抗白介素-31受体a单克隆抗体奈莫单抗在食蟹猴体内的产前和产后发育研究。

背景：奈莫单抗是一种针对白细胞介素31受体a （IL-31RA）的人源化单克隆抗体，用于治疗特应性皮炎和结节性痒疹。这些炎症性皮肤病影响广泛的年龄组，包括孕妇和儿童；然而，它们对产前和产后发育的生物学影响知之甚少。因此，我们报告并讨论了一项经nemolizumab治疗的食蟹猴产前和产后发育增强研究的结果，该研究还包括对幼年毒性的评估。方法：从妊娠第20天至分娩，每2周（双周）给药1或25 mg/kg给药Nemolizumab，以研究其对产前和产后发育的潜在毒性。此外，考虑到目标患者人群的年龄，他们的后代在出生后约1至7个月每两周皮下注射1或25 mg/kg，以调查对青少年的潜在毒性。检查包括免疫功能测试和IL-31对神经系统的影响，以及ICH S5指南中概述的标准评估，以全面评估安全性。结果：当剂量达到25 mg/kg时，母鼠和子代均未观察到nemolizumab相关的毒性。母体血浆奈莫单抗浓度在妊娠期维持良好，分娩后逐渐降低。后代的血浆浓度高于母鼠，一直维持到预定的尸检。结论：重复给药奈莫单抗阻断IL-31信号不会对食蟹猴的妊娠、分娩、哺乳或产后身体和功能发育产生不利影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Birth Defects Research Medicine-Embryology

CiteScore

3.60

自引率

9.50%

发文量

153

期刊介绍： The journal Birth Defects Research publishes original research and reviews in areas related to the etiology of adverse developmental and reproductive outcome. In particular the journal is devoted to the publication of original scientific research that contributes to the understanding of the biology of embryonic development and the prenatal causative factors and mechanisms leading to adverse pregnancy outcomes, namely structural and functional birth defects, pregnancy loss, postnatal functional defects in the human population, and to the identification of prenatal factors and biological mechanisms that reduce these risks. Adverse reproductive and developmental outcomes may have genetic, environmental, nutritional or epigenetic causes. Accordingly, the journal Birth Defects Research takes an integrated, multidisciplinary approach in its organization and publication strategy. The journal Birth Defects Research contains separate sections for clinical and molecular teratology, developmental and reproductive toxicology, and reviews in developmental biology to acknowledge and accommodate the integrative nature of research in this field. Each section has a dedicated editor who is a leader in his/her field and who has full editorial authority in his/her area.