Male and Female Fertility Assessment in the Cynomolgus Monkey Following Administration of ABT-874, a Human Anti-IL-12/23p40 Monoclonal Antibody

BACKGROUND ABT‐874 is an anti‐IL‐12/23 monoclonal antibody that binds to the p40 subunit of human IL‐12 and IL‐23. As part of its preclinical safety assessment, studies were conducted to asses its potential effects on the reproductive system in male and female cynomolgus monkeys. METHODS Sexually mature male cynomolgus monkeys (n = 6/group) were administered once weekly subcutaneous doses of 0, 5, 25, or 100 mg/kg ABT‐874 for 13 weeks. Four monkeys/group were necropsied at the end of the 13‐week dosing period and two monkeys/group were necropsied following an 8‐week recovery period. Endpoints assessed in these males included sperm parameters such as sperm count and morphology, male reproductive hormones, and testes histopathology. Sexually mature female cynomolgus monkeys (n = 6/group) were administered subcutaneous doses of 0, 5, 25, or 100 mg/kg/week ABT‐874 for two menstrual cycles, and recovery was subsequently assessed in each of these animals over two menstrual cycles. Endpoints assessed in these females included menses and reproductive hormone levels. RESULTS In both the male and female fertility studies, there were no unscheduled deaths and there was no evidence of toxicity. In male monkeys, there were no ABT‐874‐related effects on sperm count or motility, histopathology of the testes or effects on testosterone and inhibin B levels. In addition, menstrual cycle length, progesterone, 17ß‐estradiol, and luteinizing hormone levels in female monkeys were comparable among control and ABT‐874‐treated groups. CONCLUSIONS These results demonstrate that ABT‐874 had no adverse effects on reproductive hormones or fertility parameters in male or female cynomolgus monkeys.