Remicade: which tox species, and why?

“A small number of chimpanzees, the only relevant species identified for safety testing, were given single or up to 5 once daily repeated doses of infliximab.”

“infliximab could neutralise human and chimpanzee TNFα with similar potency, while TNFα from a number of other species (rhesus cynomolgous, pigtail macaque, cotton-top tamarin, baboon, marmoset, pig, rabbit, rat and mouse) was not affected by infliximab.”

“In an attempt to mimic the clinical situation of TNFα inhibition, studies were conducted in mice using a monoclonal antibody against mouse TNFα (cV1q).”

“Although single and repeated dose toxicity studies were performed in rats, these studies are not considered to have any relevance for the human safety assessment. A small number of chimpanzees, the only relevant species identified for safety testing, were given single or up to 5 once daily repeated doses of infliximab.”

“In an attempt to mimic the clinical situation of TNFα inhibition, studies were conducted in mice using a monoclonal antibody against mouse TNFα (cV1q).”

“A 6-month study in CD-1 mice was conducted to assess the tumorigenic potential of cV1q anti-mouse TNFα, an analogous antibody.”

“Data from genetically modified animals (i.e. transgenic and knock-out models) and from studies of a monoclonal antibody against mouse TNFα have provided some reassurance regarding carcinogenic potential and reproductive toxicity, although some effects on fertility were observed in mice.”