Investigation of maternal and fetal exposure to an IgG2 monoclonal antibody following biweekly intravaginal administration to cynomolgus monkeys throughout pregnancy |
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| Affiliation: | 1. Amgen Inc., Seattle, WA, United States;2. Amgen Inc., Thousand Oaks, CA, United States;3. Charles River Laboratories Preclinical Services Nevada, Reno, NV, United States;1. Department of Clinical Immunology and Allergy, Royal Adelaide Hospital, Adelaide, Australia;2. Department of Immunology, South Australian Pathology, Adelaide, Australia;3. Department of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia;4. Department of Immunology, Flinders University, Adelaide, Australia;5. Division of Health Sciences, School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, University of South Australia, Australia;1. FUNLAM, Basic Science Department, Universidad Católica Luis Amigó, Transversal 51A #67B-90, Medellín, Colombia;2. CONICET and FAMAF, Universidad Nacional de Córdoba, Medina Allende s/n, 5000 Córdoba, Argentina;1. Safety Assessment and Laboratory Animal Resources, Merck & Co., Inc., West Point, PA, United States;2. Imaging Department, Merck & Co., Inc., West Point, PA, United States |
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| 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; 100 mg/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; <25 ng/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 116 ng/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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| Keywords: | Vaginal absorption Monoclonal antibody Human risk |
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