Filspari: which tox species, and why?

“General toxicity studies were conducted for durations up to 13 weeks in mice, 26 weeks in rats, and 39 weeks in monkeys.”

“As sequence similarity of monkey ETAR and AT1R to human ETAR and AT1R is relatively high, anticipated pharmacology is observed in the monkey safety pharmacology and repeat dose toxicity studies, and considering that pharmacological activity, metabolic profile, and toxicological findings in monkeys are consistent with observations in the rat”

“Following 26 weeks of treatment in rats, minimal to mild renal tubular degeneration was noted at the 320 mg/kg/day dose with increased incidence/severity compared to the control, and it was fully reversible.”

“General toxicity studies were conducted for durations up to 13 weeks in mice, 26 weeks in rats, and 39 weeks in monkeys.”

“In embryo-fetal developmental toxicity studies in pregnant rats and rabbits, teratogenicity and developmental toxicity were observed.”

“Long-term carcinogenicity studies were conducted in mice (26 -week duration) and one in rats (104- week duration).”

“The affinity of sparsentan for the rat ETAR and AT1R was also demonstrated. Receptor homology ranges from 99% identity to human for both ETAR and AT1R in monkeys and to 92% and 94% identity for ETAR and AT1R, respectively, in mice.”