Quviviq: which tox species, and why?

“repeat dose general toxicology studies in the mouse for up to 28 days, rat for up to 26 weeks, and dog for up to 39 weeks”

“Species selection was based on pharmacologically relevant binding to Orexin receptors in humans and in these non-clinical species with high selectivity and potency, metabolically relevant pathways in these species are similar to those in humans, as well as close plasma protein binding properties for some species only.”

“In Beagle dogs were administered 10, 30, or 100mg/kg/day Daridorexant for 39 consecutive weeks”

“repeat dose general toxicology studies in the mouse for up to 28 days, rat for up to 26 weeks, and dog for up to 39 weeks”

“In animal reproduction studies, oral administration of daridorexant to pregnant rats and rabbits during the period of organogenesis did not cause fetal toxicity or malformation at doses up to 8 and 10 times the maximum recommended human dose (MRHD) of 50 mg, respectively, based on AUC.”

“Daridorexant did not increase the incidence of tumors in rats treated for 2 years at oral doses of 15, 50, and 150 mg/kg/day. The high dose of 150 mg/kg/day is approximately 4 times the MRHD of 50 mg, based on AUC. Daridorexant did not increase the incidence of tumors in Tg.rasH2 mice treated for 26 weeks”

“Rats and dogs are pharmacologically species relevant for daridorexant, as the orexin system is highly conserved across mammalian species, and as activity on sleep parameters had been clearly demonstrated.”