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

“Belzutifan was not mutagenic in the in vitro bacterial reverse mutation (Ames) test or clastogenic in the in vitro micronucleus assay in human peripheral blood lymphocytes or the in vivo bone marrow erythrocyte micronucleus test in rats.”

“presented the results of the 6-month Tg. rasH2 mouse carcinogenicity study with belzutifan at doses up to 600 mg/kg/day. The results indicate no belzutifan-related neoplastic findings at any dose level and no carcinogenic risk were identified in the study.”

“The Applicant conducted a pilot embryo-fetal development study in rats. Oral administration of belzutifan at doses up to 200 mg/kg/day to pregnant rats during the period of organogenesis caused embryo-fetal lethality (post-implantation loss) at ≥ 60 mg/kg/day”

“Belzutifan was a low-potency hERG blocker in vitro (IC50 > 50 µM) and did not influence QTc in dogs dosed up to 30 mg/kg/day for 3 months.”