Investigation of Maternal and Fetal Exposure to an IgG2 Monoclonal Antibody Following Biweekly Intravaginal Administration to Cynomolgus Monkeys Throughout Pregnancy

Reproductive Toxicology. 2014;48:132-137

Abstract: To assess the potential for male-mediated drug transfer to their female partner and/or developing conceptus, vaginal uptake of a monoclonal antibody(mAb) biotherapeutic was assessed in cynomolgus monkeys. A human IgG2 mAb (IgG2X; bound human and cynomolgus monkey neonatal Fc-receptor, FcRn, with similar high affinity) was administered intravaginally (IvG; 100mg/dose) to 5 pregnant cynomolgus monkeys biweekly from gestation day (gd) 21 to gd133. In all maternal samples collected before gd119, IgG2X plasma concentrations were below the limit of quantification (BLQ; <25ng/mL). After dosing on gd119 and 133, maternal IgG2X plasma concentrations remained BLQ in 3/5 monkeys and were very low in 2/5 (up to 116ng/mL; ∼0.01% of the IvG dose). IgG2X was BLQ in all fetal plasma samples. These data indicate that male-mediated mAb drug transfer via seminal fluid does not present a health risk to the female partner and is not bioavailable to the developing conceptus.

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