title: Developmental toxicity assessment of tanezumab, an anti-nerve growth factor monoclonal antibody, in cynomolgus monkeys (Macaca fascicularis).
abstract: Two intravenous studies with tanezumab, an anti-nerve growth factor monoclonal antibody, were conducted in pregnant cynomolgus monkeys to assess potential effects on pregnancy and pre- and postnatal development. Study 1 evaluated infants up to 12 months of age following weekly maternal dosing (0, 0.5, 4 or 30 mg/kg; 18 per group) from gestation day (GD) 20 through parturition. Study 2 evaluated infants 2 months postnatally following weekly maternal dosing (0, 0.5 or 30 mg/kg; 20-21 per group) from GD 20 through 48. In the absence of maternal toxicity, tanezumab increased stillbirth and post-birth infant mortality/morbidity, decreased infant growth and resulted in microscopic changes in the peripheral sympathetic and sensory nervous system of the infants at all doses. Decreased primary antibody responses and increased incidences in skin changes in infants were also observed. The no-observed-adverse-effect-level for maternal toxicity was 30 mg/kg and <0.5 mg/kg for developmental toxicity.
authors.affiliation: Pfizer Inc, Groton, CT, USA. Electronic address: christopher.j.bowman@pfizer.com.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Bowman
authors.affiliation: Pfizer Inc, San Diego, CA, USA. Electronic address: mark.evans@pfizer.com.
authors.forename: Mark
authors.initials: M
authors.lastname: Evans
authors.affiliation: Pfizer Inc, Groton, CT, USA. Electronic address: thomas.r.cummings@pfizer.com.
authors.forename: Thomas
authors.initials: T
authors.lastname: Cummings
authors.affiliation: SNBL USA, Ltd., Everett, WA, USA. Electronic address: soneda@snblusa.com.
authors.forename: Satoru
authors.initials: S
authors.lastname: Oneda
authors.affiliation: Tox Path Specialists, Frederick, MD, USA. Electronic address: mbutt@toxpath.net.
authors.forename: Mark
authors.initials: M
authors.lastname: Butt
authors.affiliation: Pfizer Inc, Groton, CT, USA. Electronic address: susan.hurst@pfizer.com.
authors.forename: Susan
authors.initials: S
authors.lastname: Hurst
authors.affiliation: Pfizer Inc, Groton, CT, USA. Electronic address: Jessica-lyn.gremminger@pfizer.com.
authors.forename: Jessica-Lyn
authors.initials: JL
authors.lastname: Gremminger
authors.affiliation: Pfizer Inc, South San Francisco, CA, USA. Electronic address: dave.shelton@pfizer.com.
authors.forename: David
authors.initials: D
authors.lastname: Shelton
authors.affiliation: Pfizer Inc, Groton, CT, USA. Electronic address: cris.kamperschroer@pfizer.com.
authors.forename: Cris
authors.initials: C
authors.lastname: Kamperschroer
authors.affiliation: Pfizer Inc, San Diego, CA, USA. Electronic address: mark.zorbas@pfizer.com.
authors.forename: Mark
authors.initials: M
authors.lastname: Zorbas
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000633:toxicity*; D001724:Birth Weight / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D008252:Macaca fascicularis; D008297:Male; D008431:Maternal-Fetal Exchange; D019055:No-Observed-Adverse-Effect Level; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D020800:Receptor, Nerve Growth Factor / Q000037:antagonists & inhibitors; D012867:Skin / Q000187:drug effects / Q000473:pathology; D050497:Stillbirth
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D020800:Receptor, Nerve Growth Factor; C549319:tanezumab
keywords: Developmental toxicity; Monoclonal antibody; Nerve growth factor; Non-human primate; Pregnancy; Tanezumab