Nucala: which tox species, and why?

“The nonclinical program with mepolizumab was conducted in Cynomolgus monkeys, which were determined to be the only pharmacologically relevant nonclinical test species.”

“The species specificity of mepolizumab was restricted to human and nonhuman primate IL-5 only. Mepolizumab did not bind to mouse or rat IL-5.”

“Fertility and embryofetal development were evaluated with male and female CD-1 mice treated with SB264091, a rat anti-human IL-5 surrogate monoclonal antibody (lgG2b), which cross reacts with human and murine IL-5.”

“The nonclinical program with mepolizumab was conducted in Cynomolgus monkeys, which were determined to be the only pharmacologically relevant nonclinical test species.”

“Development and reproductive endpoints were evaluated as part of the 6-month chronic toxicology study of mepolizumab in monkeys (fertility based on histopathology of male and female reproductive organs), a pre- and postnatal development study of mepolizumab in pregnant female cynomolgus monkeys, and a study in mice that were treated with a surrogate monoclonal antibody (IgG2b).”

“The need for a carcinogenicity study was discussed with the Executive Carcinogenicity Assessment Committee and it was concluded that a carcinogenicity study was not required given the lack of related findings in the 6-month toxicology study in monkeys and since conduct of a study in rodents did not appear to be technically feasible.”

“Fertility and embryofetal development were evaluated with male and female CD-1 mice treated with SB264091, a rat anti-human IL-5 surrogate monoclonal antibody (lgG2b), which cross reacts with human and murine IL-5.”