title: Developmental and peri-postnatal study in cynomolgus monkeys with belimumab, a monoclonal antibody directed against B-lymphocyte stimulator.
abstract: Belimumab is a fully human monoclonal antibody antagonist for soluble B-lymphocyte stimulator, and is a potential therapeutic for various autoimmune disorders. To support clinical use, belimumab was administered intravenously to pregnant cynomolgus monkeys every 2 weeks throughout gestation at dosages of 5 and 150 mg/kg. Fetuses were delivered by C-section on Gestation Day 150 from one-half of the mothers, and evaluated for teratologic effects (external, visceral, skeletal, and heart), pharmacodynamics (PD) and toxicokinetics (TK). Remaining mothers delivered their infants naturally, enabling extensive assessment of PD and TK during a 1-year postnatal period. Effects attributed to belimumab were limited to the expected pharmacology, primarily decreased numbers of B-lymphocytes in peripheral blood of mothers and infants, and in fetal lymphoid tissues. Infants demonstrated full recovery upon cessation of exposure. In conclusion, belimumab was well tolerated at pharmacologically active dose levels in pregnant cynomolgus monkeys and their infants after exposure throughout pregnancy.
authors.affiliation: Charles River Preclinical Services Nevada, 6995 Longley Lane, Reno, NV 89511, USA. diana.auyeung-kim@crl.com
authors.forename: Diana J
authors.initials: DJ
authors.lastname: Auyeung-Kim
authors.forename: Madhav N
authors.initials: MN
authors.lastname: Devalaraja
authors.forename: Thi-Sau
authors.initials: TS
authors.lastname: Migone
authors.forename: Wendy
authors.initials: W
authors.lastname: Cai
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Chellman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D019540:Area Under Curve; D053264:B-Cell Activating Factor / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D005333:Fetus / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000276:immunology / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008252:Macaca fascicularis / Q000196:embryology* / Q000254:growth & development*; D008431:Maternal-Fetal Exchange / Q000187:drug effects / Q000276:immunology; D008657:Metabolic Clearance Rate; D011247:Pregnancy; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053264:B-Cell Activating Factor; D007166:Immunosuppressive Agents; C511911:belimumab