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

“No standard genotoxicity battery of studies was performed with ipilimumab.”

“considering the lack of relevance of the rodent species for ipilimumab, the limited value of short-term carcinogenicity studies with homologous products (as reflected in the draft reviewed version of the guideline), and the advanced condition intended to be treated by ipilimumab, the lack of conventional carcinogenicity studies is acceptable.”

“Beginning in the third trimester, administration of ipilimumab at doses resulting in exposures approximately 2.6 to 7.2 times the human exposure at a dose of 3 mg/kg resulted in dose-related increases in abortion, stillbirth, premature delivery (with corresponding lower birth weight), and an increased incidence of infant mortality.”

“No drug-related findings were observed in standard clinical evaluations of cardiovascular, respiratory or neurologic function (including behaviour, posture, coordination, neurologic exams that included peripheral and cranial nerve evaluations, peripheral reflexes, proprioception, or eye movements, and in the 1-month study, electrocardiograms) conducted in monkeys as part of the repeat-dose toxicity studies for up to 6 months with ipilimumab.”

“No standard genotoxicity battery of studies was performed with ipilimumab.”

“No standard genotoxicity battery of studies was performed with ipilimumab.”

“No standard genotoxicity battery of studies was performed with ipilimumab.”

“Carcinogenicity studies for ipilimumab were not conducted.”

“In addition, considering the lack of relevance of the rodent species for ipilimumab, the limited value of short-term carcinogenicity studies with homologous products (as reflected in the draft reviewed version of the guideline), and the advanced condition intended to be treated by ipilimumab, the lack of conventional carcinogenicity studies is acceptable.”

“No drug-related findings were observed in standard clinical evaluations of cardiovascular, respiratory or neurologic function (including behaviour, posture, coordination, neurologic exams that included peripheral and cranial nerve evaluations, peripheral reflexes, proprioception, or eye movements, and in the 1-month study, electrocardiograms) conducted in monkeys as part of the repeat-dose toxicity studies for up to 6 months with ipilimumab.”