Cimzia: which tox species, and why?

“Based on the species specificity of target binding, the cynomolgus monkey has been selected as the main species for toxicity testing.”

“Certolizumab pegol did not bind TNFα from rodents, rabbit, guinea pigs and dog, but it inhibited TNFα from non-human primates, with at least a 1000-fold lower activity than against hTNFα.”

“Instead, the homologous agent cTN3 PF, which is a chimeric Fab' fragment conjugated to 40 kDa PEG, was tested in the reproductive and developmental toxicity studies.”

“The pivotal repeat dose toxicity studies consisted of a 26-week repeat-dose toxicity study and a 52-week immunotoxicity study, both performed in cynomolgus monkeys.”

“Since certolizumab pegol does not cross-react with mouse or rat TNFα, reproduction studies were performed in rats using a rodent anti-murine TNFα pegylated Fab fragment (cTN3 PF), similar to certolizumab pegol.”

“No conventional carcinogenicity testing was performed with certolizumab pegol, which was acceptable considering the nature of the compound and the lack of pharmacological activity and immunogenicity of certolizumab pegol in species normally used for such testing.”

“Instead, the homologous agent cTN3 PF, which is a chimeric Fab’ fragment conjugated to 40 kDa PEG, was tested in the reproductive and developmental toxicity studies.”