Evrysdi: which tox species, and why?

“Repeated dose toxicity studies included studies in Wistar Hannover rats (adults) and cynomolgus monkeys (sexually immature), with administration of risdiplam, by daily oral gavage, during up to 26 and 39 weeks, respectively.”

“The choice of the animal species was justified based on secondary mRNA splice targets and on metabolism. The SMN2 gene is human-specific.”

“Repeated dose toxicity studies included studies in Wistar Hannover rats (adults) and cynomolgus monkeys (sexually immature), with administration of risdiplam, by daily oral gavage, during up to 26 and 39 weeks, respectively.”

“Repeated dose toxicity studies included studies in Wistar Hannover rats (adults) and cynomolgus monkeys (sexually immature), with administration of risdiplam, by daily oral gavage, during up to 26 and 39 weeks, respectively.”

“Embryofetal development in rat and rabbit - Pre- and postnatal development in rat - 4-week preweaning juvenile development in rat - 13-week postweaning juvenile development in rat”

“A 6-month carcinogenicity study in Tg.rasH2 mice showed no tumorigenic effects at oral doses up to 9 mg/kg/day, which was associated with exposures (AUC) of 15600 and 11800 ng.hr/mL in males and females, respectively.”

“However, the use of the available transgenic mouse models of SMA for toxicity testing was not considered appropriate due to lack of availability in sufficiently large numbers, lack of suitable characterisation of relevant physiological parameters”