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

“Vadadustat was negative for mutagenicity in the Ames assay. Vadadustat yielded clastogenic activity from two in vitro assays but was negative for genotoxic activity when administered to Sprague Dawley rats in an in vivo COMET and chromosomal aberration study.”

“Vadadustat was not carcinogenic in RasH2 transgenic mice and was not carcinogenic in Sprague Dawley rats administered vadadustat up to approximately 0.3-fold the clinical dose of 600 mg, based on AUC.”

“Vadadustat did not affect fertility or cause teratogenicity, although lower fetal weight (-7%), lower pup weight (-5% to -11%), and reduced fetal skeletal ossifications occurred at dose levels associated with maternal toxicity.”

“In both rat and dog, vadadustat caused a transient decrease in blood pressure with a compensatory increase in HR. Vadadustat had no meaningful effect in the in vitro hERG assay and did not cause changes of P-QRS-T complexes in rats or dogs.”