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

“Pralsetinib was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay or clastogenic in either the in vitro micronucleus assay in TK6 cells or the in vivo bone marrow micronucleus assay in rats.”

“The Applicant did not conduct carcinogenicity or fertility studies to support the currently proposed indication (NSCLC), and these studies are not needed to support a marketing application for a drug intended to treat patients with advanced cancer.”

“In the EFD study, multiple visceral and skeletal malformations were observed, as well as developmental variation, even from the lowest dose level of 5 mg/kg/day. 100% post implantation loss was seen at 20 mg/kg/day and above.”

“Pralsetinib did not inhibit in vitro hERG potassium currents at relevant concentrations or induce QTc prolongation in the 13-week repeat-dose study in cynomolgus monkeys. Single oral administration of ≥25 mg/kg pralsetinib resulted in increased blood pressure with concomitant decreases in heart rate in male Sprague-Dawley rats.”