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

“Although the Ames and micronucleus assays were negative for the induction of genetic toxicity, there was an increase in structural abnormalities in the chromosome aberration assay.”

“Although the Sponsor did not definitively identify the MOA for tumor development in rodents, the overall weight of evidence indicates that the rodent liver neoplasms were most likely mediated by rodent-specific CAR activation which is not relevant in humans.”

“Embryofetal development studies revealed increased fetal resorptions and altered morphological development in rats and rabbits at exposures greater than 100-fold and 7-fold, respectively, the exposure at the MRHD.”

“Observations included inhibition of the hERG current at > 50-fold the MRHD, prolongation of the QRS, QT, and QTc levels in dogs at 11-fold following intravenous though not oral dosing, and in NHPs at >15-fold the MRHD.”