Inqovi: which tox species, and why?

“In the general toxicology studies, cedazuridine (mice and cynomolgus monkeys) and decitabine (rats) were administered orally once daily for 5 to 7 days in 28-day cycles, similar to the clinical regimen.”

“A literature assessment submitted by the Applicant concluded that humans, mice, and cynomolgus monkeys have similar CDA tissue distribution and activity profiles, and CDA activity was notably absent in rats.”

“Pivotal studies of oral decitabine monotherapy were limited to a 13-week/4-cycle study conducted in rats only (up to 7.5 mg/kg/dose).”

“Toxicokinetics (TK) were also evaluated as part of the general toxicology studies for cedazuridine (in mice and cynomolgus monkeys) and decitabine (in rats).”

“No stand-alone reproductive and developmental toxicology studies were conducted with cedazuridine or ASTX727. Decitabine is teratogenic, fetotoxic, and embryotoxic based on its mechanism of action and animal studies described in the product label for decitabine for injection”

“No carcinogenicity studies have been conducted with ASTX727 or with its active components, cedazuridine and decitabine.”

“A literature assessment submitted by the Applicant concluded that humans, mice, and cynomolgus monkeys have similar CDA tissue distribution and activity profiles, and CDA activity was notably absent in rats.”