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

“Odevixibat tested negative in the bacterial reverse mutation (Ames) assay, the in vitro mouse lymphoma cell forward mutation assay, and the in vivo rat micronucleus test.”

“In the 2-year carcinogenicity studies, odevixibat was not tumorigenic in rats or mice at oral doses up to 100 mg/kg/day.”

“No adverse findings were observed in the fertility study in male and female Wistar rats, the embryo-fetal development study in rats, or the juvenile toxicity study in rats. In an embryo-fetal development study in pregnant rabbits, fetuses from all maternal groups treated orally with odevixibat showed an increase in cardiovascular malformations”

“There were no nonclinical safety issues of significant concern as assessed by the secondary pharmacology screens or the cardiovascular, respiratory, central nervous system, gastrointestinal, or renal safety pharmacology studies conducted during the development program.”

“Odevixibat tested negative in the bacterial reverse mutation (Ames) assay, the in vitro mouse lymphoma cell forward mutation assay, and the in vivo rat micronucleus test.”

“Odevixibat tested negative in the bacterial reverse mutation (Ames) assay, the in vitro mouse lymphoma cell forward mutation assay, and the in vivo rat micronucleus test.”

“Odevixibat tested negative in the bacterial reverse mutation (Ames) assay, the in vitro mouse lymphoma cell forward mutation assay, and the in vivo rat micronucleus test.”

“In the 2-year carcinogenicity studies, odevixibat was not tumorigenic in rats or mice at oral doses up to 100 mg/kg/day.”

“In the 2-year carcinogenicity studies, odevixibat was not tumorigenic in rats or mice at oral doses up to 100 mg/kg/day.”

“Odevixibat did not affect the hERG potassium channel at the tested concentration (1 μM), which is 7700-fold higher than the IC50 (0.13 nM) in the human IBAT transfected cell assay (0062SZ).”