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

“Mobocertinib was not mutagenic in an in vitro bacterial reverse mutation assay and did not cause chromosomal aberrations in an in vitro chromosome aberration assay in human peripheral blood lymphocytes. Mobocertinib was not clastogenic in an in vivo bone marrow micronucleus test in rats.”

“FDA agrees that carcinogenicity studies are not needed to support the use of mobocertinib in the currently proposed indication per ICH S9.”

“Mobocertinib induced embryo-fetal mortality due to post-implantation loss (early resorptions) as well as decreased fetal weight at 10 mg/kg (approximately 1.7 times the exposure based on AUC at the human dose of 160 mg).”

“Mobocertinib and its metabolites AP32914 and AP32960 inhibited the human ether-a-go-go related gene (hERG) current at concentrations > 5 µM, suggesting a low potential for QT prolongation.”