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

“Asciminib was not genotoxic in an in vitro bacterial mutagenicity (Ames) assay, an in vitro micronucleus assay in human peripheral blood lymphocytes (HPBL) or an in vivo rat peripheral blood reticulocyte micronucleus assay.”

“In a 2-year carcinogenicity study, rats were administered oral doses of asciminib at 20, 66, and 200 mg/kg/day in males and 10, 30, and 66 mg/kg/day in females. Asciminib induced a statistically significant increase in the incidence of benign Sertoli cell tumors in the ovaries of high-dose females.”

“Malformations were evident at 150 mg/kg and included cleft palate, anasarca (edema), and cardiac abnormalities.”

“The IC50 for asciminib in the hERG patch clamp was 11.4 µM. This translates into a clinical safety margin > 200- or > 100- or 30- fold when compared to free exposure in subjects at dose of 40 mg BID or 80 mg QD or 200 mg BID, respectively.”