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

“Ensartinib was not mutagenic in a bacterial reverse mutation (Ames) assay and was not clastogenic in an in vitro human lymphocyte chromosome aberration assay or an in vivo rat bone marrow micronucleus assay.”

“Carcinogenicity studies were not conducted or needed to support the use of ensartinib in the currently proposed indication per International Council for Harmonisation (ICH) S9.”

“Oral administration of ensartinib to pregnant rats during the period of organogenesis caused adverse developmental outcomes, including embryo-fetal mortality, alterations to growth, and structural abnormalities. Adverse embryo-fetal findings were seen at maternal exposures approximately equivalent to the human exposure at the recommended dose of 225 mg/day based on AUC”

“male dogs dosed with 20/15 mg/kg/day ensartinib (approximately 1.6-fold the human exposure based on AUC at the clinical dose of 225 mg/day) in the 13-week toxicology study exhibited a statistically significant 10% increase in QTc prolongation compared to controls, which resolved during the recovery period.”