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

“no genotoxicity studies were performed with evinacumab, per ICH S6.”

“The Applicant submitted a weight of evidence carcinogenicity assessment for evinacumab based on available evidence from relevant literature and completed animal toxicology studies, which suggested that there is no identified risk of carcinogenicity for evinacumab.”

“The reproductive toxicity of evinacumab was assessed using male and female fertility endpoints collected from the chronic 26-week monkey toxicity study, and by conducting combined female fertility/early embryonic/pre and postnatal development study in rats, embryofetal development studies in rats and rabbits”

“Safety pharmacology studies were integrated into pivotal GLP repeat dose toxicology studies of evinacumab conducted in rats and cynomolgus monkeys.”

“Evinacumab is not expected to interact directly with DNA and mutagenicity studies are not appropriate for this reason.”

“Evinacumab is not expected to interact directly with DNA and mutagenicity studies are not appropriate for this reason.”

“Evinacumab is not expected to interact directly with DNA and mutagenicity studies are not appropriate for this reason.”

“The Applicant submitted a weight of evidence assessment to address the carcinogenic potential of evinacumab, which was based on information available from relevant literature and animal toxicology studies completed under the IND.”

“No in vivo animal carcinogenicity studies were requested by the Division after consulting with CDER’s Executive Carcinogenicity Assessment Committee (April 18, 2017) and the sponsor’s carcinogenicity assessment is considered adequate.”

“Administration of evinacumab at up to 100 mg/kg/week (SC or IV) for 5 and 26 consecutive weeks (in rats and monkeys, respectively), did not result in any test article-related cardiovascular (heart rate, blood pressure, and electrocardiography), respiratory (breaths/minute and pulse oximetry), or CNS (neurobehavioral observation battery) effects.”