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

“Genotoxicity studies with biologics such as garadacimab are not required.”

“Based on the weight of evidence, the Division agreed with the Applicant that a rodent carcinogenicity study was not technically feasible. Further, there appears to be a low or negligible carcinogenic potential based on the results of the 26-week monkey study and review of the published literature regarding chronic inhibition of FXIIa.”

“For the F1 generation, no garadacimab-related effects were observed on mortality, clinical signs, body weight, developmental signs, functional observation battery, eye-blink response, presence of motile sperm, reproductive performance, cesarean section parameters, or preweaning or postweaning macroscopic observations.”

“Safety pharmacology parameters were incorporated into the pivotal repeat-dose 26-week monkey toxicology study. With intravenous (IV) doses up to 100 mg/kg/week and subcutaneous (SC) doses up to 200 mg/kg/week, no treatment-related effects on electrocardiogram, blood pressure, respiration rate, or pulse rate were observed during the 26-week Treatment Period.”