Vonjo: which tox species, and why?

“Mice and dogs were considered the most relevant nonclinical species for toxicological evaluations based on the similarity of their pacritinib metabolic profile to humans and the sufficient bioavailability observed in these nonclinical species.”

“Mice and dogs were considered the most relevant nonclinical species for toxicological evaluations based on the similarity of their pacritinib metabolic profile to humans and the sufficient bioavailability observed in these nonclinical species.”

“there were no cardiovascular effects attributed to the administration of pacritinib in the repeat-dose toxicity study in dogs dosed up to 14.2 mg/kg BID for 39 weeks.”

“Toxicological characterization of pacritinib was assessed in mice (1, 4, and 26 weeks), rats (1, 4, and 13 weeks), dogs (1, 4, and 39 weeks) and rabbits (embryo-fetal development) during repeat-dose toxicology studies.”

“Reproductive toxicology was assessed in mice in two fertility and early embryonic development studies (BALB/c and CD-1), an embryo-fetal development study (CD-1) and a pre- and postnatal development study (CD-1). An embryo-fetal development study was also conducted in New Zealand white rabbits.”

“Pacritinib was not carcinogenic in either a 2-year rat study or during a 26-week hemizygous Tg(HRAS) transgenic mouse study, demonstrating low carcinogenic potential secondary to inhibition of JAK2/FLT3 activity.”

“there were no cardiovascular effects attributed to the administration of pacritinib in the repeat-dose toxicity study in dogs dosed up to 14.2 mg/kg BID for 39 weeks.”