Veozah: which tox species, and why?

“Repeat dose toxicity studies were conducted in intact female rats and cynomolgus monkeys.”

“Cynomolgus monkey was selected as the relevant nonrodent species as nonhuman primates are anatomically and functionally similar to humans in the reproductive system, which is known to be affected by LH change. In addition, according to the in vitro radioligand assay, fezolinetant has a similar affinity for the human and cynomolgus monkey NK3 receptor orthologs.”

“In the 26-week rat study (Study No 8331724), fezolinetant was administered orally by daily gavage to sexually mature female rats at a dose of 0 (vehicle), 30, 100, or 200 mg/kg.”

“Repeated dose toxicity studies were conducted in rats up to 26 weeks and in monkeys up to 39 weeks.”

“In embryo-fetal development toxicity studies in rats and rabbits, embryo-lethality was noted at the highest doses (128- and 174-fold the human AUC 24 at the human therapeutic dose for rats and rabbits, respectively).”

“Carcinogenicity of fezolinetant was investigated in the 104-week carcinogenicity study with Wistar rats administered the test substance at the dose levels of 10, 30 and 100 mg/kg/day by oral gavage, and in the 26-week study with transgenic RasH2 mice.”

“Fezolinetant has a similar affinity for human and monkey NK3 receptors and 8-fold less for rat NK3 receptors.”