Tremfya: which tox species, and why?

“The applicant submitted one single dose and one pivotal 5-week (IV/SC)/24-week (SC) repeat dose toxicity studies in cynomolgus monkey”

“Guselkumab demonstrated comparable species binding to IL-23 from humans, non-human primates (including cynomolgus monkeys), and guinea pigs, but only partial or no binding to dog, mouse, or rat IL-23.”

“The influence of guselkumab administration on fertility was assessed in female and male Guinea Pigs that were dosed 50 or 100 mg/kg guselkumab subcutaneously twice a week.”

“The applicant submitted one single dose and one pivotal 5-week (IV/SC)/24-week (SC) repeat dose toxicity studies in cynomolgus monkey and one 3-week SC toxicity and tolerability study in guinea pigs with guselkumab.”

“The following pharmacology/toxicology studies were reviewed under IND 105004 except “SC Fertility and Early Embryonic Development Study in Male Guinea Pigs (Study # T-2014-021)” and “Enhanced Pre- and Post-natal Development Study in the Cynomolgus Monkey with a 6-Month Postnatal Evaluation (Study # 20029626)”.”

“Guselkumab cannot be tested in a traditional 2-year rodent study to evaluate its carcinogenic potential due to its species specific binding in monkeys and/or guinea pigs.”

“Thus, cynomolgus monkeys and guinea pigs were selected as the pharmacologically relevant species for use in nonclinical studies with guselkumab.”