title: Investigation of maternal and fetal exposure to an IgG2 monoclonal antibody following biweekly intravaginal administration to cynomolgus monkeys throughout pregnancy.
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.
authors.affiliation: Amgen Inc., Seattle, WA, United States. Electronic address: gmoffat@amgen.com.
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Moffat
authors.affiliation: Amgen Inc., Seattle, WA, United States.
authors.forename: Rhian
authors.initials: R
authors.lastname: Davies
authors.affiliation: Amgen Inc., Seattle, WA, United States.
authors.forename: Gayle
authors.initials: G
authors.lastname: Kwon
authors.affiliation: Amgen Inc., Thousand Oaks, CA, United States.
authors.forename: Marc W
authors.initials: MW
authors.lastname: Retter
authors.affiliation: Charles River Laboratories Preclinical Services Nevada, Reno, NV, United States.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Chellman
authors.affiliation: Amgen Inc., Thousand Oaks, CA, United States.
authors.forename: Sekhar
authors.initials: S
authors.lastname: Kanapuram
authors.affiliation: Amgen Inc., Thousand Oaks, CA, United States.
authors.forename: Meghan
authors.initials: M
authors.lastname: Moore
authors.affiliation: Amgen Inc., Thousand Oaks, CA, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Loomis
authors.affiliation: Amgen Inc., Thousand Oaks, CA, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Amgen Inc., Thousand Oaks, CA, United States.
authors.forename: Ian T G
authors.initials: IT
authors.lastname: Pyrah
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology*; D008252:Macaca fascicularis; D008297:Male; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D012661:Semen / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G
keywords: Human risk; Monoclonal antibody; Vaginal absorption