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

“Metabolite CC1084037 was negative in an Ames assay, and positive in an in vitro chromosomal aberration assay in human (TK6) cells but negative in an in vivo rat micronucleus/comet assay.”

“Oral administration of ozanimod (0, 8, 25, or 80 mg/kg/day) to Tg.rasH2 mice for 26-weeks resulted in an increase in hemangioma and hemangiosarcoma (combined) in males and females at the mid and high doses tested. Oral administration of ozanimod (0, 0.2, 0.7, or 2 mg/kg/day) to rats for 2 years resulted in no increase in tumors.”

“There were no effects on fertility in male or female animals dosed with ozanimod. Embryolethality and developmental effects (e.g., incomplete skeletal ossification, malpositioned vertebrae, malformed or absent arteries, anasarca, malpositioned testes, and cleft palate) occurred in pregnant rats and/or rabbits exposed to ozanimod and its metabolites during gestation.”

“Cardiovascular: In a GLP in vitro hERG assay, ozanimod and the major human metabolite, CC112273, were determined to be potent hERG inhibitors (IC50 of 0.2 and 0.6 µM, respectively; 100503.SJD, 170531.SFD).”