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

“Vepdegestrant and its major metabolite ARV-473 did not induce mutations in the bacterial reverse mutation (Ames) assay. Vepdegestrant was not clastogenic in the in vitro human lymphocyte micronucleus assay or in the in vivo micronucleus study in rats.”

“Administration of ARV-471 did not result in statistically significant ovarian tumors in transgenic rasH2 mice at daily doses up to 800 mg/kg/day for 6 months.”

“Oral administration of vepdegestrant resulted in embryo-fetal mortality (increased resorptions, post-implantation loss and reduced number of live fetuses) at ≥30 mg/kg/day (0.3 times the human AUC at the recommended dose).”

“Vepdegestrant did not demonstrate adverse cardiovascular, respiratory, or functional observational battery (FOB) effects in standalone safety pharmacology studies or repeated-dose toxicology studies in rats and dogs at the tested doses.”