Nubeqa: which tox species, and why?

“The Applicant conducted general toxicology studies to evaluate the effects of daily oral administration of darolutamide in rats for up to 26 weeks and in dogs for up to 39 weeks.”

“In terms of pharmacokinetics, the qualitative metabolite profiles of darolutamide in rats as well as the overall biotransformation pathways seem to be quite comparable to the profiles obtained in human plasma. However, the metabolite profiles of darolutamide between dogs and human are different.”

“Dogs received twice daily oral darolutamide at doses of 25, 75 or 200 mg/kg/dose (50, 150 or 400 mg/kg/day; n=4/sex/group [main], 2/sex/group [recovery for VH and HD only]).”

“The Applicant conducted general toxicology studies to evaluate the effects of daily oral administration of darolutamide in rats for up to 26 weeks and in dogs for up to 39 weeks.”

“No embryo-fetal development toxicology studies were conducted or warranted to support this NDA submission, as the proposed indication does not include females.”

“In the absence of relevant data to adequately assess the carcinogenicity potential of darolutamide, the applicant will submit results of a 6-month Tg-rasH2 mouse study (see RMP).”