Attruby: which tox species, and why?

“There were no histopathology findings consistent with kidney injury in chronic toxicology studies in two non-human species (Study 20141689, 26-week toxicity study in rats and Study 21141692, 39-week toxicity study in dogs)”

“Overall, there was no significant difference observed in PK profiles between animals and humans that would limit the interpretation of animal toxicology studies and the nonclinical species used were considered appropriate for the safety of acoramidis and its metabolites in human.”

“Repeat-dose toxicity studies were conducted in rats for up to 26 weeks with oral dose levels ranging from 50 to 1000 mg/kg/day.”

“Repeated dose toxicity studies comprised studies in rats and dogs with once daily administration of acoramidis by oral gavage during up to 26 and 39 weeks, respectively.”

“Developmental and reproductive toxicology studies comprised studies on male and female fertility and early embryonic development, in rats, embryo-fetal development, in rats and rabbits, and pre- and post-natal development, in rats.”

“A two-year oral carcinogenicity study in rats did not identify any carcinogenic potential at doses up to 50 mg/kg/day (males) or 350 mg/kg/day (females), doses producing exposures that approximated the clinical AUC or were 11-times the clinical AUC, respectively, at the MRHD. No acoramidis-related tumors were observed in a 26-week oral carcinogenicity study in Tg rasH2 mice.”

“Repeat-dose toxicity studies were conducted in rats for up to 26 weeks with oral dose levels ranging from 50 to 1000 mg/kg/day.”