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

“Pemigatinib was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay or clastogenic in either the in vitro chromosomal aberration assay in human peripheral blood lymphocytes or the in vivo bone marrow micronucleus assay in rats.”

“Carcinogenicity studies were not conducted or needed to support the use of pemigatinib in the currently proposed indication per ICH S9.”

“Once daily oral administration of pemigatinib to pregnant rats during the period of organogenesis (gestation Days 6 to 17) resulted in reduced maternal body weight and food consumption at dose levels ≥0.3 mg/kg (approximately 0.6 times the exposure based on AUC at the human dose of 13.5 mg) accompanied by 100% post-implantation loss (early resorptions).”

“Pemigatinib inhibited the hERG potassium current with an IC50 >8 µM, which is not clinically achievable at the recommended dose of 13.5 mg. Consistent with this in vitro finding, pemigatinib did not induce QTc prolongation in a single-dose safety pharmacology study in cynomolgus monkeys or in the 13-week repeat-dose study in monkeys.”