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

“Linerixibat did not cause gene mutation or chromosomal damage in a bacterial mutagenicity assay (Ames test), a chromosomal aberration assay using Chinese hamster ovary cells, or an in vivo rat bone marrow micronucleus assay”

“Linerixibat was not tumorigenic in a 2-year oral carcinogenicity study in rats with oral administration of up to 1,000 mg/kg/day (approximately 3,900 times the recommended dose based on AUC). In a 26-week oral carcinogenicity study in TgRasH2 mice, no drug-related tumors were observed following administration of linerixibat up to 160 mg/kg/day.”

“Reproductive and developmental toxicology studies using oral administration of linerixibat included a fertility study in male and female rats, embryo-fetal development studies in rats and rabbits, and a pre- and postnatal development study in rats.”

“Linerixibat, at concentrations up to the limit of solubility (253.73 μM, 138.71 μg/mL) did not inhibit human ether-a go-go-related gene (hERG) current recorded from human embryonic kidney cells (HEK293) expressing the hERG ion channel.”

“Linerixibat did not cause gene mutation or chromosomal damage in a bacterial mutagenicity assay (Ames test), a chromosomal aberration assay using Chinese hamster ovary cells, or an in vivo rat bone marrow micronucleus assay”

“Linerixibat did not cause gene mutation or chromosomal damage in a bacterial mutagenicity assay (Ames test), a chromosomal aberration assay using Chinese hamster ovary cells, or an in vivo rat bone marrow micronucleus assay”

“Linerixibat did not cause gene mutation or chromosomal damage in a bacterial mutagenicity assay (Ames test), a chromosomal aberration assay using Chinese hamster ovary cells, or an in vivo rat bone marrow micronucleus assay”

“Linerixibat was not tumorigenic in a 2-year oral carcinogenicity study in rats with oral administration of up to 1,000 mg/kg/day (approximately 3,900 times the recommended dose based on AUC). In a 26-week oral carcinogenicity study in TgRasH2 mice, no drug-related tumors were observed following administration of linerixibat up to 160 mg/kg/day.”

“A two-year carcinogenicity study in Wistar Han rats was conducted in support of the marketing authorization for linerixibat.”

“Linerixibat, at concentrations up to the limit of solubility (253.73 μM, 138.71 μg/mL) did not inhibit human ether-a go-go-related gene (hERG) current recorded from human embryonic kidney cells (HEK293) expressing the hERG ion channel.”