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

“Finerenone was also negative in the in vitro chromosomal aberration assay in mammalian cells and in the in vivo mouse micronucleus test.”

“Two-year carcinogenicity studies conducted in mice and rats showed no significant increase in neoplasms in males or females in either study; the CDER Exec CAC concurred with this conclusion.”

“In the embryo-fetal toxicity study in rats, finerenone resulted in reduced placental weights and signs of fetal toxicity, including reduced fetal weights and retarded ossification at the maternal toxic dose of 10 mg/kg/day, corresponding to an AUC unbound of 19 times that in humans.”

“Finerenone showed no adverse effects on CNS parameters and respiratory functions (rat), on hemodynamic/ECG parameters (dog), and on cardiac repolarization in vitro (hERG K+ current).”

“finerenone did not induce gene mutations by base-pair changes or frame-shifts in the genome of five S. typhimurium strains when tested up to a maximum recommended dose of 5.0 mg/plate in the absence and presence of S9 mix.”

“Finerenone was also negative in the in vitro chromosomal aberration assay in mammalian cells and in the in vivo mouse micronucleus test.”

“Finerenone was also negative in the in vitro chromosomal aberration assay in mammalian cells and in the in vivo mouse micronucleus test.”

“Two-year carcinogenicity studies conducted in mice and rats showed no significant increase in neoplasms in males or females in either study; the CDER Exec CAC concurred with this conclusion.”

“a full battery of reproductive toxicology studies (including a fertility and early embryonic development study in rat, embryofetal developmental toxicity studies in rat and rabbit and a pre-and postnatal development study in rat), and two 2-year carcinogenicity studies in mouse and rat.”

“The hERG IC50 was 86 µmol/L (33 mg/L), which is approximately 200 times the total clinical Cmax (161 µg/L), and 2400 times the free fraction (Cmax, unbound 13.4 µg/L; fu 8.3%).”