Rezdiffra: genotox, carcinogenicity and repro: done or skipped?

“Resmetirom was not mutagenic or clastogenic in the Ames test, the in vitro chromosomal aberration test using cultured human peripheral blood lymphocytes, the in vitro micronucleus test using L5178Y tk+/- mouse lymphoma cells, or the in vivo rat micronucleus assay.”

“In a 2-year carcinogenicity study in mice, resmetirom at 100 mg/kg/day (51 times the maximum recommended dose based on AUC) produced a statistically significant increase in combined incidence of leiomyoma (benign) and leiomyosarcoma (malignant) in uterus”

“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. No effects on fertility and early embryonic development were observed at 30 mg/kg/day”

“A single oral administration of resmetirom at doses up to 300 mg/kg in rats had no significant effect on neurobehavioral or respiratory functions. Resmetirom at concentrations up to 30 µmol/L produced 18.2% inhibition of human Ether-à-go-go-related gene current.”