Scemblix: what was done before first-in-human, and what came after?

“CABL001X2101 Countries: Australia, France, Germany, Italy, Japan, Singapore, South Korea, Spain, The Netherlands, United States”

“The selection of the starting dose of asciminib was based on 4-week GLP toxicology studies conducted in rats and dogs.”

“The starting dose of asciminib for patients with CML-CP/-AP selected for the dose escalation part of this study was set at 10 mg orally administered BID under fasted conditions. The selection of the starting dose of asciminib was based on 4-week GLP toxicology studies conducted in rats and dogs.”

“Prolonged administration of asciminib (3, 15, and 50 mg/kg/day) for 39 weeks in cynomolgus monkeys induced comparable findings to those observed in the 13-week study”

“The safety of asciminib was assessed in general toxicology (dogs, rats and monkeys up to 4, 26 and 39 weeks, respectively)”

“The potential for reproductive and/or developmental toxicity of asciminib was investigated in a study on fertility and early embryonic development in the rat and studies on embryo-foetal development in rats and rabbits.”

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

“Pre- and postnatal development: A pre- and postnatal development study has not been performed and is not considered necessary to support the proposed indication.”

“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.”

“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.”

“Carcinogenicity studies have not been conducted in accordance with ICH S9.”