Filspari: genotox, carcinogenicity and repro: done or skipped?

“There was no evidence of mutagenicity or clastogenicity for sparsentan in in vitro bacteria reverse mutation and chromosomal aberration assays or in an in vivo rat micronucleus study.”

“In the 2-year rat carcinogenicity study, there was no evidence of an increased incidence of neoplasia in male rats orally administered 15 mg/kg/day (dose limited by tolerability) and in female rats orally administered up to 240 mg/kg/day, which provides an exposure approximately 0.7 times and 26 times the AUC at the MRHD, respectively.”

“In pregnant rats treated with sparsentan at doses of 80, 160, and 240 mg/kg/day, dose-dependent toxicity and teratogenicity marked by craniofacial malformations, skeletal abnormalities, embryo-fetal lethality, and reduced fetal weight were observed at all doses.”

“Sparsentan, at doses up to 1000 mg/kg, did not show statistically significant or biologically relevant AEs on the CVS (monkeys) or the respiratory and CNS (rats).”

“There was no evidence of mutagenicity or clastogenicity for sparsentan in in vitro bacteria reverse mutation and chromosomal aberration assays or in an in vivo rat micronucleus study.”

“There was no evidence of mutagenicity or clastogenicity for sparsentan in in vitro bacteria reverse mutation and chromosomal aberration assays or in an in vivo rat micronucleus study.”

“There was no evidence of mutagenicity or clastogenicity for sparsentan in in vitro bacteria reverse mutation and chromosomal aberration assays or in an in vivo rat micronucleus study.”

“In the 2-year rat carcinogenicity study, there was no evidence of an increased incidence of neoplasia in male rats orally administered 15 mg/kg/day (dose limited by tolerability) and in female rats orally administered up to 240 mg/kg/day, which provides an exposure approximately 0.7 times and 26 times the AUC at the MRHD, respectively.”

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

“Sparsentan did not inhibit the hERG channel (hERG safety margin >2912x) and no QTc prolongation was detected in the in vivo QT study in monkeys at 6× the high clinical exposure.”