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

“In genetic toxicology studies, elacestrant was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay or, clastogenic in either in vitro chromosome aberration assays or an in vivo rat bone marrow micronucleus assay.”

“Carcinogenicity studies were not conducted with elacestrant in accordance with ICH S9 guidance; however, of note, in the rat 26-week repeat dose toxicology study B-granulosa cell tumor was observed at ≥25 mg/kg/day”

“Elacestrant was embryo lethal and teratogenic when administered to pregnant rats at ≤30 mg/kg via daily oral gavage during the period of organogenesis on gestational days 6 through 17 followed by cesarean section on gestational day 21.”

“Elacestrant blocked the hERG channel up to approximately 87% at 1 µM (IC50= 0.41 µM) and led to a complete block of the cardiac action potential of rabbit Purkinje fibers at 10 µM.”