Voydeya: which tox species, and why?

“Toxicological characterization of danicopan was evaluated in beagle dogs (5 days, 2-weeks, 13- weeks, 13-weeks, and 9 months), wistar han (WH) rats (14 days, 28-days, 13-weeks, and 6- months)”

“The dog was selected as the nonrodent nonclinical safety species (repeat-dose toxicology), and the off-target activity/toxicity of danicopan was assessed in rats.”

“In the 6-month toxicity study in rats (species not pharmacologically sensitive to danicopan), hypertrophy in liver, thyroid and adrenal gland was observed at doses of 1000 mg/kg/day (~26-fold above human exposure at 200 mg three times a day based on AUC).”

“Toxicological characterization of danicopan was evaluated in beagle dogs (5 days, 2-weeks, 13- weeks, 13-weeks, and 9 months), wistar han (WH) rats (14 days, 28-days, 13-weeks, and 6- months)”

“Danicopan is pharmacologically active in the rabbit and is therefore considered toxicologically relevant for the assessment of fertility and early embryonic developmental (FEED) toxicity, Embryo/Fetal Developmental (EFD) toxicity and Pre- and Post-natal Developmental (PPND) toxicity.”

“Danicopan was not carcinogenic in the 6-month carcinogenicity study in the TgRasH2 mouse model. Danicopan was not carcinogenic in the 2-year rat carcinogenicity study at exposures 15- to 23-times the exposure at the MRHD (based on AUC).”

“Beagle dogs and NZW rabbits are considered pharmacologically relevant nonclinical species for toxicological evaluations based on the in vitro/in vivo/ex vivo assessments of danicopan PD activity.”