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

“Genotoxicity and carcinogenicity studies are generally not appropriate for biotechnology-derived monoclonal antibodies such as burosumab. No genotoxicity or carcinogenicity studies have been conducted by the Applicant; this is endorsed.”

“Overall, it is agreed that the carcinogenicity risk of burosumab appears to be low.”

“The Applicant’s proposed NOAEL at 3 mg/kg for pre- and postnatal development in fetuses and offspring is agreed with. It is also agreed that burosumab did not induce teratogenicity in monkeys up to a dose of 30 mg/kg.”

“Safety pharmacology studies were not performed in separate studies, but safety pharmacology parameters (respiratory rate, ECG, blood pressure and cardiac function) were assessed in 14- and 40- week repeat-dose toxicity studies in adult and juvenile cynomolgus monkeys”