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

“Clascoterone did not display clear genotoxic potential in a standard battery of genetic toxicity studies. Clascoterone was not mutagenic in an in vitro reverse bacterial mutation assay or clastogenic in an in vitro chromosome aberration assay.”

“Clascoterone cream (0.1%, 1%, or 5%) was not carcinogenic after daily topical administration in a 2-year carcinogenicity study in rats.”

“a developmental NOAEL could not be determined because clascoterone-related malformations were noted in three fetuses at the low dose (LD) and 1 fetus each at the mid dose (MD) and HD.”

“In a pilot hERG assay, clascoterone produced low potency dose-related inhibition of the hERG potassium current (up to 40% inhibition at the highest concentration evaluated [10μM])”

“Clascoterone did not display clear genotoxic potential in a standard battery of genetic toxicity studies. Clascoterone was not mutagenic in an in vitro reverse bacterial mutation assay or clastogenic in an in vitro chromosome aberration assay.”

“On the basis of available in vitro studies, clascoterone can be considered negative in the prokaryotic cell gene mutation assay, and equivocal in in vitro the micronucleus test.”

“In a micronucleus assay in rats, a single subcutaneous dose of clascoterone produced a slight, statistically significant increase in bone marrow micronuclei at the high dose (2000 mg/kg), but not lower doses (500 mg/kg and 1000 mg/kg); this result was considered equivocal”

“Clascoterone cream (0.1%, 1%, or 5%) was not carcinogenic after daily topical administration in a 2-year carcinogenicity study in rats.”

“Clascoterone cream (0.1%, 1%, or 5%) was not carcinogenic after daily topical administration in a 2-year carcinogenicity study in rats.”

“The safety pharmacology studies reported that clascoterone can be considered a low-potency hERG-channel inhibitor, but the highest concentration tested is 1500 times higher than the highest plasma concentration measured in the clinical studies (7.65 ng/mL). The in vivo study conducted in dogs at a maximal dose of 250 mg/kg was negative.”