Orgovyx: which tox species, and why?

“The repeat-dose toxicity studies for relugolix were conducted in mice (up to 13 weeks), rats (up to 26-weeks) and monkeys (up to 39 weeks) using the intended oral route of administration.”

“The cynomolgus monkey was selected as the non-rodent species because of the high sequence homology with the human GnRH receptor (97.5% compared to 92.1% in dog) and the similar affinity and potency at the GnRH receptor relative to dogs.”

“In a 39-week study, relugolix (1.5, 5, 15, or 50 mg/kg/day) was administered by oral gavage to cynomolgus monkeys followed by a 13-week recovery period.”

“The repeat-dose toxicity studies for relugolix were conducted in mice (up to 13 weeks), rats (up to 26-weeks) and monkeys (up to 39 weeks) using the intended oral route of administration.”

“Reproductive and developmental toxicology studies were conducted in rats and rabbits.”

“Two-year carcinogenicity studies were conducted in mice at oral relugolix doses up to 100 mg/kg/day and in rats at doses up to 600 mg/kg/day.”

“As relugolix has only low affinity for the mouse GnRH receptor, a human GnRHR knock-in mice was generated, in which mouse GnRHR was replaced by human GnRHR, to evaluate the effect of relugolix on a hypothalamic-pituitary-gonadal axis.”