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

“Abrocitinib was not mutagenic in an in vitro reverse bacterial mutation assay. Abrocitinib was positive in an in vitro micronucleus assay and determined to be an aneugen in a follow-up study; however, it was not genotoxic in an in vivo micronucleus assay in rats.”

“At doses ≥10 mg/kg/day, abrocitinib significantly increased the incidence of benign thymoma in the thymus of female rats. No abrocitinib-related tumor findings were noted in males.”

“Abrocitinib increased the incidence of skeletal variations at doses ≥30 mg/kg/day, including the incidence of short 13th ribs, thickened ribs (HD only), and cervical arches with reduced ventral processes (HD only). Abrocitinib increased embryofetal lethality at the HD.”

“In vitro, abrocitinib did not produce clinically relevant inhibition of the hERG potassium current or the Nav1.5 sodium current. Up to 300 µM abrocitinib produced 78% inhibition of the hERG current (IC50: 95 µM) and 31% inhibition of the Nav1.5 current.”