Gavreto: which tox species, and why?

“The Applicant evaluated the safety of pralsetinib using Sprague-Dawley rats and Cynomolgus monkeys in GLP-compliant repeat-dose toxicology studies of up to 13 weeks duration.”

“The dog was also investigated as a non-rodent species, but due to species specific toxicities, related to p38 MAPK inhibition, and exacerbated toxicities following this inhibition, the dog was not suitable for further toxicity studies beyond single dose or 7 days repeat-dose studies.”

“In the GLP-compliant 13-week repeated-dose toxicology study in rats (10 animals/sex/group), pralsetinib was administered at oral doses of 5, 10, and 20 mg/kg/day.”

“The Applicant evaluated the safety of pralsetinib using Sprague-Dawley rats and Cynomolgus monkeys in GLP-compliant repeat-dose toxicology studies of up to 13 weeks duration.”

“With respect to reproductive toxicity studies, a fertility and early embryonic development study and an extended dose range EFD study were performed 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 GLP-compliant 13-week repeated-dose toxicology study in rats (10 animals/sex/group), pralsetinib was administered at oral doses of 5, 10, and 20 mg/kg/day.”