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

“Lemborexant was not mutagenic in the in vitro bacterial reverse mutation (Ames) assay or in the in vitro mouse lymphoma thymidine kinase assay, and was not clastogenic in the in vivo rat micronucleus assay.”

“Lemborexant did not increase the incidence of tumors in a 6-month carcinogenicity study in Tg ras H2 transgenic mice or in a 2-year study in rats and therefore is considered non-carcinogenic.”

“Reproductive and developmental toxicity was assessed in fertility studies in male and female rats, embryo-fetal development studies in pregnant rats and rabbits, and a pre- and post-natal development study in rats. Irregular estrous cycles and decreased pregnancy rates were observed in female rats at doses ≥100 mg/kg/day.”

“Lemborexant prolonged the QTc interval in conscious telemetered monkeys after single doses ≥30 mg/kg, which produces exposures approximately 22-fold the steady state Cmax value in humans at the maximum recommended human dose (MRHD).”