Nulibry: which tox species, and why?

“Repeat-dose toxicity studies in juvenile rats for 13 and 26 weeks and in juvenile dogs for 39 weeks (Table 15).”

“The MoCo-synthesis is considered highly conserved between species, and cPMP is considered identical between species. Thus, rat and dog are considered relevant species for toxicity studies.”

“In the 39-week toxicity study in juvenile dogs in which fosdenopterin HBr (coded ALXN1101) was administered at 1, 3, 5, and 10 mg/kg/day once daily, no adverse effects were observed.”

“Repeat-dose toxicity studies in juvenile rats for 13 and 26 weeks and in juvenile dogs for 39 weeks (Table 15).”

“fosdenopterin to pregnant rabbits once daily during the period of organogenesis (GD 7 to GD 20) at doses up to 200 mg/kg/day (approximately 89 times the human exposure at the MRHD, based on AUC) did not result in adverse developmental effects. In a pre- and postnatal development study, subcutaneous administration of fosdenopterin to pregnant mice”

“Carcinogenicity studies with fosdenopterin have not been conducted. A carcinogenicity study in a single species will be conducted as a postmarketing requirement.”