Prolia: which tox species, and why?

“Since denosumab recognizes and neutralizes RANKL in non human primates, the cynomolgus monkey was identified as a relevant species and the main studies have been conducted in ovariectomized animals.”

“This absence is acceptably justified by the fact that the RANKL domain to which denosumab binds is entirely conserved between cynomolgus monkeys and humans.”

“Several studies have been conducted with a transgenic huRANKL knock-in mouse model expressing chimeric RANKL that can be recognized and neutralized by denosumab.”