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

“Fezolinetant showed no genotoxic potential by the bacterial reverse mutation test, chromosomal aberration test, or in vivo micronucleus test.”

“In a 2-year female rat carcinogenicity study and a 26-week carcinogenicity study in rasH2 transgenic mice, there was no evidence of drug-related carcinogenicity at 186-fold and 47-fold the human AUC 24 at the human therapeutic dose of 45 mg, respectively.”

“In embryo-fetal toxicity animal studies with fezolinetant, embryo-lethality occurred at high doses above the human therapeutic dose in rats and rabbits, but no teratogenicity was observed. In the pre- and post-natal development animal study, delayed parturition and embryo-lethality occurred at high doses above the human therapeutic dose in rats.”

“This translates into a 350-fold difference between human free Cmax at MRHD and IC50 value in hERG assay, indicating that no effects on the cardiovascular system with regard to ventricular repolarization and proarrhythmic risk are to be expected in humans.”