Lupkynis: which tox species, and why?

“The rat and monkey were determined to be the most appropriate toxicological species, given the emetic effect observed in dogs.”

“agrees based on the higher systemic exposure (and consequently, higher sensitivity) observed in the rat and the more similar metabolic profile of the monkey compared to humans. The reviewer agrees the emetic effect in the dog would lead to drug exposure inconsistencies and problems with data interpretation.”

“As most studies were performed using mix-ISA247, a bridging programme was performed with voclosporin which included a 13-week study in the rat.”

“This was demonstrated in some of the studies that used cyclosporine A as a comparator including the pivotal 26-week study in rats and 39- week study in monkeys.”

“There were no test article related malformations or variations seen in fetuses from the developmental toxicity studies with rats or rabbits. In a prenatal and postnatal development study with mix-ISA247 in rats, dystocia (observed as prolonged parturition) was observed at 25 mg/kg/day.”

“Two-year studies were conducted in rats and mice.”

“As most studies were performed using mix-ISA247, a bridging programme was performed with voclosporin which included a 13-week study in the rat.”