Orladeyo: which tox species, and why?

“General toxicity studies included chronic oral toxicity studies in rats and monkeys (treatment durations of up to 26 and 39 weeks, respectively).”

“monkey and rat plasma with mean EC50s of 5.4, 5.2, and 7.2 nM (Study BR-7353-005-REV-01), supporting the suitability of monkey and rat as the non-clinical species used for toxicology studies.”

“Cynomolgus monkeys (4/sex/dose) were dosed by oral gavage with 0, 1, 2.5, 7.5, and 20 mg/kg/day berotralstat for 39 weeks.”

“General toxicity studies included chronic oral toxicity studies in rats and monkeys (treatment durations of up to 26 and 39 weeks, respectively).”

“The completed package of reproductive and developmental toxicity for BCX7353 includes a fertility and early embryonic development study in male and female rats, embryo-foetal development (EFD) studies in rats and in rabbits, and a pre- and post-natal development study in rats.”

“The carcinogenicity potential of berotralstat was evaluated in a 2-year traditional bioassay in rats and a 26-week study in B6F1 Tg.RasH2 mice.”

“Furthermore, BCX7353 was shown to inhibit kallikrein activity ex-vivo, in activated human plasma from healthy human volunteers and in monkey and rat plasma with mean EC50s of 5.4, 5.2, and 7.2 nM (Study BR-7353-005-REV-01), supporting the suitability of monkey and rat as the non-clinical species used for toxicology studies.”