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

“Vonoprazan was not genotoxic in the bacterial reverse mutation assay, an in vitro chromosomal aberration assay in Chinese Hamster lung cells, and an in vivo rat bone marrow micronucleus test.”

“In a 2-year carcinogenicity study in mice and rats, hepatocellular adenomas and carcinomas and drug-related increases in benign and malignant neuroendocrine cell tumors in the stomachs were noted.”

“In the embryofetal development study in rats, fetal abnormalities were limited to the 300 mg/kg/day dose and included ventricular septal defect and mal-positioned subclavian artery in fetuses, as well as tail abnormalities and small anal opening.”

“The IC50 for the inhibitory effect of vonoprazan on human Ether-à-go-go-Related Gene (hERG) current was 4.8 mcg/mL, which is more than 100-fold higher than the mean maximum plasma concentration (Cmax) for the 20 mg dose vonoprazan in humans.”