Effects of tanezumab on satellite glial cells in the cervicothoracic ganglion of cynomolgus monkeys: A 26-week toxicity study followed by an 8-week recovery period.

Tanezumab, a humanized monoclonal anti-NGF antibody, has demonstrated efficacy and safety profiles in Phase III clinical trials of chronic pain. In a 24-week study in non-human primates, morphological observations of sympathetic ganglia showed decreased ganglia volume, decreased neuronal size, and increased glial cell density compared with controls after 3 tanezumab treatments. Using stereological techniques to quantify glial cells, the present 26-week study found no significant difference after weekly treatments in total cervicothoracic ganglia satellite glial cell number between placebo- or tanezumab-treated cynomolgus monkeys. These findings suggest that tanezumab treatment does not result in a true gliosis in sympathetic ganglia.

Developmental toxicity assessment of tanezumab, an anti-nerve growth factor monoclonal antibody, in cynomolgus monkeys (Macaca fascicularis).

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.