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

“Genetic toxicology studies were not needed to support the development and approval of risankizumab, per the ICH S6(R1) guidance.”

“Overall the risk for malignancy associated with long-term inhibition of IL-23 following administration of risankizumab to humans is considered to be low.”

“However, as compared to the control group, a dose-dependent increase in fetal/infant loss was noted in the risankizumab-treated groups. The percent fetal/infant loss was 19%, 32%, and 43% in the vehicle control, 5 mg/kg, and 50 mg/kg groups, respectively.”

“Intravenous treatment with doses up to 50 mg/kg/week risankizumab for 4 weeks did not cause treatment-related effects on neurological or cardiovascular functions in Cynomolgus monkeys.”

“Therefore, genotoxicity testing was not carried out in line with ICH S6(R1) and this is acceptable.”

“Therefore, genotoxicity testing was not carried out in line with ICH S6(R1) and this is acceptable.”

“Therefore, genotoxicity testing was not carried out in line with ICH S6(R1) and this is acceptable.”

“Conventional rodent carcinogenicity studies were not conducted for the evaluation of the carcinogenic potential of risankizumab, as rodents are not a pharmacologically relevant species.”

“Concurrence has been received from the Executive Carcinogenicity Assessment Committee of CDER that a 2-year rodent carcinogenicity study is not needed.”

“Intravenous treatment with doses up to 50 mg/kg/week risankizumab for 4 weeks did not cause treatment-related effects on neurological or cardiovascular functions in Cynomolgus monkeys.”