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

“Baxdrostat was not genotoxic when tested in a battery of in vitro and in vivo assays.”

“The carcinogenic potential of baxdrostat was evaluated in 6-month transgenic mouse and 2-year rat studies. There was no evidence of carcinogenicity with oral doses up to 45 mg/kg/day in mice (264-fold), and up to 10 mg/kg/day in male rats (105-fold) and up to 3 mg/kg/day in female rats (62-fold).”

“In embryofetal development studies, reduced maternal body weight gain and fetal toxicities were observed in rats (adverse skeletal malformations of skull: mandible/zygomatic arch fusion) and rabbits (decrease in fetal body weight) at exposures >54-fold and >29-fold relative to the clinical exposures at the MRHD.”

“Baxdrostat inhibited the hERG tail current with an IC50 of 360 μM, approximately 15,000-fold above the free Cmax at the clinical dose of 2 mg. A trend toward persistent QTc prolongation (+7%) was observed at 6 hours post-dose in single-dose telemetry study in monkeys at 50 mg/kg.”