Takhzyro: which tox species, and why?

“Due to high anti-drug antibody (ADA) response in rats that reduced drug exposure, and combined with the apparent similarity in toxicity profile in rats and cynomolgus monkey, the cynomolgus monkey was selected as the single species for the pivotal 6-month toxicity study.”

“DX-2930 inhibits human, rat, and cynomolgus monkey pKal activity with comparable potencies (Table 2). Rats and cynomolgus monkeys are pharmacologically relevant species.”

“Rat and cynomolgus monkey were used as toxicology species based on in vitro pharmacology potency studies which indicated that pKal inhibition in rat and monkey was similar to human pKal inhibition.”

“Due to high anti-drug antibody (ADA) response in rats that reduced drug exposure, and combined with the apparent similarity in toxicity profile in rats and cynomolgus monkey, the cynomolgus monkey was selected as the single species for the pivotal 6-month toxicity study.”

“Complete reviews of the pivotal 39-week general toxicology study in monkeys, 13-week fertility study in male and female monkeys, and an enhanced pre- and postnatal development (ePPND) toxicology study conducted in monkeys are included”

“The conduct of carcinogenicity studies in rodents was not feasible based on the development of ADA in SD rats after repeated dosing.”

“Rat and cynomolgus monkey were used as toxicology species based on in vitro pharmacology potency studies which indicated that pKal inhibition in rat and monkey was similar to human pKal inhibition.”