Qfitlia: which tox species, and why?

“Repeat-dose toxicology studies were conducted in healthy rats for up to 26 weeks, healthy monkeys for up to 39 weeks, and in hemophilia mice for up to 26 weeks.”

“Fitusiran is pharmacologically active in mice, rats, monkeys, and dogs because the antithrombin mRNA sequences are highly conserved across species.”

“To address the limitations of studies in healthy animals, the Applicant conducted extensive studies in animal models of hemophilia”

“Repeat-dose toxicology studies were conducted in healthy rats for up to 26 weeks, healthy monkeys for up to 39 weeks, and in hemophilia mice for up to 26 weeks.”

“Because hemophilia is primarily an X-linked disease, no embryo-fetal toxicity studies in rats and rabbits have been performed.”

“The Sponsor submitted final reports for carcinogenicity studies of fitusiran 1. A 26-week study in TgRasH2 mouse study-at3-glp17-001.pdf, 2. A 2-year study in rats study-car0186.pdf.”

“Fitusiran is pharmacologically active in mice, rats, dogs, and cynomolgus monkeys, as the AT mRNA target sequence is fully conserved (mice, rats, monkeys) or highly conserved (dogs) with the human sequence.”