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

“Maralixibat was not mutagenic or clastogenic in the Ames test, the in vitro chromosomal aberration test using Chinese hamster ovary cells, or the in vivo rat micronucleus assay.”

“Maralixibat chloride was not tumorigenic in a 2-year oral carcinogenicity study in rats with administration of up to 100 mg/kg/day (approximately 233 to 870 times the maximum recommended dose based on AUC). In a 26-week oral carcinogenicity study in TgRasH2 mice with doses of up to 25 (males) or 75 (females) mg/kg/day, no drug-related tumors were observed”

“Reproductive and developmental toxicology studies included a fertility study in male and female rats, embryo-fetal development studies in rats and rabbits, and a pre- and post-natal development study in rats. Two juvenile animal toxicity studies were performed in rats. No adverse findings were observed in the reproductive and developmental toxicology studies.”

“had no significant effect on neurobehavioral functions in rats, cardiovascular function in dogs, or respiratory function in guinea pigs. Maralixibat at concentrations up to 1 µmol/L did not inhibit hERG current.”

“Maralixibat was not mutagenic or clastogenic in the Ames test, the in vitro chromosomal aberration test using Chinese hamster ovary cells, or the in vivo rat micronucleus assay.”

“Maralixibat was not mutagenic or clastogenic in the Ames test, the in vitro chromosomal aberration test using Chinese hamster ovary cells, or the in vivo rat micronucleus assay.”

“Maralixibat was not mutagenic or clastogenic in the Ames test, the in vitro chromosomal aberration test using Chinese hamster ovary cells, or the in vivo rat micronucleus assay.”

“Maralixibat chloride was not tumorigenic in a 2-year oral carcinogenicity study in rats with administration of up to 100 mg/kg/day (approximately 233 to 870 times the maximum recommended dose based on AUC). In a 26-week oral carcinogenicity study in TgRasH2 mice with doses of up to 25 (males) or 75 (females) mg/kg/day, no drug-related tumors were observed following administration of maralixibat chloride.”

“Therefore, submission of the 2-year rat carcinogenicity study should be a Postmarketing Requirement. The study results will be included in subsection 13.1 of the labeling, in addition to the results of the completed carcinogenicity study in Tg.RasH2 mice.”

“Maralixibat at concentrations up to 1 µmol/L did not inhibit hERG current.”