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.”

“Abrocitinib was not mutagenic in the bacterial mutagenicity assay (Ames assay).”

“Although abrocitinib was aneugenic in the in vitro TK6 micronucleus assay, abrocitinib was not aneugenic or clastogenic in an in vivo rat bone marrow micronucleus assay.”

“Although abrocitinib was aneugenic in the in vitro TK6 micronucleus assay, abrocitinib was not aneugenic or clastogenic in an in vivo rat bone marrow micronucleus assay.”

“Carcinogenicity studies were conducted in mice (6-month study in Tg rasH2 mice) and rats (104-week study).”

“Carcinogenicity studies were conducted in mice (6-month study in Tg rasH2 mice) and rats (104-week study).”

“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.”