Developmental toxicity assessment of tanezumab,an anti-nerve growth factor monoclonal antibody,in cynomolgus monkeys (Macaca fascicularis) |
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| Institution: | 1. Pfizer Inc, Groton, CT, USA;2. Pfizer Inc, San Diego, CA, USA;3. SNBL USA, Ltd., Everett, WA, USA;4. Tox Path Specialists, Frederick, MD, USA;5. Pfizer Inc, South San Francisco, CA, USA;1. Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, 15 Parkman Street, Wang ACC #435, Boston, MA 02114, USA;2. Vascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Charlestown Navy Yard, Building 149, 13th Street, Suite 9019, Boston, MA 02129, USA;1. Department of Hand and Foot Surgery, Shandong Provincial Hospital, Shandong University, 324 Jingwu Road, Jinan 250021, Shandong, China;2. Department of Hand and Foot Surgery, Enze Hospital of Taizhou Enze Medical Center (Group), No. 1 Tongyang Road, Luqiao District, Taizhou 318000, Zhejiang, China;3. Department of Hand and Foot Surgery, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan 250012, Shandong, China;4. Department of Hand and Foot Surgery, The Fourth People’s Hospital of Shanxi Province, 512 Xianningdong Road, Xian 710043, Shanxi, China;5. Department of Hand Surgery, Weinan Hand and Foot Surgery Hospital, 150 Laocheng Road, Weinan 714000, Shanxi, China;1. Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, P.O. Box 533, H-6701 Szeged, Hungary;2. Department of Obstetrics and Gynaecology, University of Szeged, P.O. Box 533, H-6701 Szeged, Hungary;1. Dipartimento di Scienze della Vita e dell’Ambiente, Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, Italy;2. Department of Occupational and Environmental Medicine, Copenhagen University Hospital, 2400 København NV, Denmark;3. Department of Laboratory Medicine, Lund University Hospital, SE-221 85 Lund, Sweden;4. Reproductive Medicine Centre, Malmö University Hospital, SE 205 02 Malmö, Sweden;5. Lund University, Department of Translational Medicine, SE 205 02 Malmö, Sweden;6. Department of Occupational Medicine, Aarhus University, Aarhus C, 8000 Aarhus, Denmark;1. Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, China;2. Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Peking University Health Science Center, China |
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| 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. |
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| Keywords: | Tanezumab Nerve growth factor Monoclonal antibody Developmental toxicity Pregnancy Non-human primate |
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