Rezdiffra: which tox species, and why?

“repeat-dose oral toxicology studies (mouse studies of up to 3 months, rat studies of up to 6 months, and dog studies of up to 9 months)”

“since the bioavailability in monkey was determined to be approximately 3%, it was not selected as a suitable”

“In the 9-month oral toxicity study in beagle dogs, resmetirom at ≥45 mg/kg/day (7 times the maximum recommended dose based on AUC) produced a significant increase in ALT, AST, total ALP, liver ALP, and bone ALP.”

“repeat-dose oral toxicology studies (mouse studies of up to 3 months, rat studies of up to 6 months, and dog studies of up to 9 months)”

“Reproductive and developmental toxicology studies of resmetirom included a fertility study in male and female rats, EFD studies in rats and rabbits, and a pre- and postnatal development study in rats.”

“genetic toxicology studies (Ames test, in vitro chromosomal aberration assay, and in vivo rat micronucleus assay), and carcinogenicity studies in mice and rats.”

“The most frequently observed effects were decreases in T4 (total and free), T3 (total and free), and TSH. These effects were observed in all general toxicology studies in rats, mice, and dogs and were likely related to the pharmacological activity of resmetirom.”