Jideytro: which tox species, and why?

“The Applicant evaluated the safety of zidesamtinib administered orally twice daily in GLP-compliant 28-day and 13-week repeat-dose general toxicology studies in Wistar-Han rats and Beagle dogs.”

“The Wistar-Han rat and beagle dog were selected as appropriate species for toxicity based on having metabolite profiles similar to human (inclusive of the main des-ethyl metabolite in patients designated M9) and ability to achieve adequate systemic exposure.”

“The Applicant evaluated the safety of zidesamtinib administered orally twice daily in GLP-compliant 28-day and 13-week repeat-dose general toxicology studies in Wistar-Han rats and Beagle dogs.”

“The Applicant evaluated the safety of zidesamtinib administered orally twice daily in GLP-compliant 28-day and 13-week repeat-dose general toxicology studies in Wistar-Han rats and Beagle dogs.”

“No fertility, early embryonic development, prenatal, or postnatal development studies were conducted with zidesamtinib, and no studies are planned per International Conference on Harmonization (ICH) S9. In a GLP embryo-fetal development study in rats (Table 15), selective developmental toxicity was observed”

“Consistent with concepts described in the ICH S9 guidance (U.S. Food and Drug Administration, 2010), carcinogenicity studies were not conducted with zidesamtinib, nor were they warranted.”

“The Applicant evaluated the safety of zidesamtinib administered orally twice daily in GLP-compliant 28-day and 13-week repeat-dose general toxicology studies in Wistar-Han rats and Beagle dogs.”