Blincyto: which tox species, and why?

“General toxicology studies included non-terminal repeat-dose studies of intravenous administration of blinatumomab in chimpanzees and repeat-dose studies of subcutaneous and intravenous administration of a murine surrogate in mice.”

“Blinatumomab bound to B and T lymphocytes from human and chimpanzee peripheral blood mononuclear cells (PBMC) but it did not bind to PBMC from the mouse, rat, beagle dog, squirrel monkey, African Green monkey, cynomolgus monkey, rhesus monkey, and baboon.”

“Because blinatumomab binds only to human and chimpanzee CD3 and CD19, the Applicant generated the murine surrogate muS103new for toxicology studies in mice and compared its activity to blinatumomab.”

“General toxicology studies included non-terminal repeat-dose studies of intravenous administration of blinatumomab in chimpanzees and repeat-dose studies of subcutaneous and intravenous administration of a murine surrogate in mice.”

“In an embryo-foetal developmental toxicity study performed in mice, the murine surrogate crossed the placenta to a limited extent (foetal-to-maternal serum concentration ratio < 1%) and did not induce embryo-foetal toxicity or teratogenicity.”

“As it is being developed for advanced cancer indications, no carcinogenicity studies have been conducted, in accordance with ICH S9.”

“Because blinatumomab binds only to human and chimpanzee CD3 and CD19, the Applicant generated the murine surrogate muS103new for toxicology studies in mice and compared its activity to blinatumomab.”