Darzalex: which tox species, and why?

“The toxicology program for daratumumab consisted of a GLP 6-week repeat-dose toxicity study in chimpanzees, and in vitro tissue cross-reactivity studies using chimpanzee and human tissues.”

“Daratumumab binds to human and chimpanzee CD38, but not to CD38 of species typically used for nonclinical toxicology testing, ie, mouse, rat, rabbit, pig, and cynomolgus and rhesus monkey.”

“Additional supportive studies were conducted with HuMab-CD38, a mAb that binds cynomolgus CD38, and included a pilot, non-GLP 2-week repeat-dose toxicity study in cynomolgus monkeys, and an in vitro tissue cross-reactivity study with cynomolgus monkey tissues.”

“The toxicology program for daratumumab consisted of a GLP 6-week repeat-dose toxicity study in chimpanzees, and in vitro tissue cross-reactivity studies using chimpanzee and human tissues.”

“No developmental and reproductive toxicity studies were performed. Developmental and reproductive toxicity testing is not feasible in chimpanzees.”

“ICH S9 also outlines that carcinogenicity studies are not warranted to support marketing for therapeutics intended to treat patients with advanced cancer, and as such no carcinogenicity studies were needed.”

“Additional supportive studies were conducted with HuMab-CD38, a mAb that binds cynomolgus CD38, and included a pilot, non-GLP 2-week repeat-dose toxicity study in cynomolgus monkeys, and an in vitro tissue cross-reactivity study with cynomolgus monkey tissues.”