Nulibry: what was done before first-in-human, and what came after?

“A total of 24 subjects was randomized into three sequential cohorts (6 active: 2 placebo) and received a single IV infusion of fosdenopterin at doses of 0.075, 0.25, and 0.68 mg/kg.”

“A 9-Month Intravenous Toxicity Study in Juvenile Beagle Dogs With a 3-Month Recovery Period”

“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”

“Nonclinical reproductive and developmental toxicity studies with fosdenopterin have not been conducted. These studies will be conducted as a postmarketing requirement.”

“Pre- and postnatal development (PPND) study in mice. • 104-Week carcinogenicity study in mice. • Thorough QT/QTc Study. We are not requiring these studies pre-approval so as not to further delay approval of Nulibry”

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

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

“A two-year carcinogenicity study in mice is however planned as a post-marketing requirement from FDA.”