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

“Sofpironium bromide was not mutagenic or clastogenic in the bacterial reverse mutation assay, in vitro mammalian chromosome aberration assay, and rat in vivo micronucleus assay.”

“The carcinogenic potential of sofpironium bromide was assessed in a 2-year dermal mouse carcinogenicity study and a 2-year subcutaneous rat carcinogenicity study. There were no drug-related neoplasms associated with daily topical administration of sofpironium bromide topical gel to mice at doses of up to 20% sofpironium bromide”

“The maternal and fetal survival, growth and development NOAEL was 10 mg/kg/day in embryo-fetal development studies in rats following sc administration. In rabbits, the NOAEL for embryo-fetal development toxicity was 2 mg/kg/day sc sofpironium bromide and the NOAEL for fetal malformation was 10 mg/kg/day.”

“In vitro, sofpironium bromide was shown to inhibit the Ikr current in a hERG assay with an IC50 value of >300 μM, an approximate 350-fold higher exposure than that was measured clinically.”