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”

“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.”

“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.”

“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.”

“No genotoxicity or carcinogenicity studies have been conducted by the Applicant; this is endorsed. The Applicant has submitted a carcinogenicity risk assessment document, summarizing and discussing relevant literature data, as well as data from in house toxicology studies.”

“The Executive Carcinogenicity Assessment Committee was consulted by the Division regarding the Sponsor’s carcinogenicity risk assessment on April 28, 2017, and concurred that carcinogenicity studies with burosumab are not needed.”

“No ECG effects were observed in the 14-week study or in the 40-week study in juvenile monkeys.”