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

“Crinecerfont was not mutagenic in the in vitro bacterial reverse mutation test (Ames) or clastogenic in the in vitro mammalian chromosomal aberrations assay in human peripheral blood lymphocytes or in the in vivo rat bone marrow micronucleus assay.”

“Crinecerfont did not show oncogenic effects in transgenic mice. In the 2-year rat study, crinecerfont increased the incidence of thyroid gland follicular cell adenoma and carcinoma in females at 100 mg/kg crinecerfont (4-fold MRHD exposure).”

“No developmental toxicity was observed in rats at 4-fold higher than human exposure at the maximum recommended human dose (MRHD) based on area under the concentration-time curve (AUC). Crinecerfont was associated with a low incidence of poly-malformations (craniofacial defects) in rabbits at 2-fold higher than human exposure at the MRHD.”

“Crinecerfont showed no potential for clinical arrhythmia risk based on human ether-à-go-go-related gene (hERG) current (<5% inhibition) or isolated rabbit Purkinje fiber action potential assays at up to 10µM crinecerfont concentrations.”