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

“Brensocatib was found to be negative for genotoxic potential in the in vitro bacterial reverse mutation (Ames) assay, an in vitro mouse lymphoma cell thymidine kinase locus assay, and in vivo micronucleus assay in rats.”

“No neoplastic findings were observed in a 6-month Tg Ras mouse study and a 104-week carcinogenicity study in rats up to the highest doses tested yielding AUC-based (unbound brensocatib fraction) safety margins of > 60-fold (mice) and > 50-fold (rat) to the MRHD.”

“Drug-related adverse skeletal malformation of bent scapula was observed in fetuses from pregnant dams administered 100 mg/kg/day brensocatib (4 of 110 fetuses, 3.7%).”

“Safety pharmacology studies indicated that brensocatib did not affect the central nervous system or respiratory system in Han Wistar rats at oral doses up to 200 mg/kg”