Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary There are no available data on GOHIBIC use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Placental transfer of monoclonal antibodies such as GOHIBIC is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy. In an enhanced pre- and post-natal (ePPND) study conducted in cynomolgus monkeys, placental transport of GOHIBIC was observed but there was no evidence of fetal harm following intravenous administration of GOHIBIC throughout pregnancy at doses 2.5 times the maximum recommended human dose (MRHD) of 800 mg on a mg/kg basis (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk for major birth defects and miscarriage in clinical recognized pregnancies is 2% - 4% and 15% - 20%, respectively. Data Animal Data In the ePPND study, pregnant cynomolgus monkeys received GOHIBIC from GD20 to GD22 (dependent on pregnancy determination), at the beginning of organogenesis, and once every 7 days until the end of gestation at intravenous doses up to 50.6 mg/kg/wk (2.5 times the MRHD on a mg/kg basis). There were no GOHIBIC-related adverse effects on maternal health, pregnancy outcome, embryo-fetal development, or neonatal growth and development up to 6 months of age (PND183). GOHIBIC crossed the placenta in cynomolgus monkeys and GOHIBIC plasma concentrations were similar in infants relative to maternal animals on PND28 and were 8-12 times higher in infants relative to maternal animals on PND91. GOHIBIC was not detected in infant plasma on PND183.