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

“Genetic toxicology battery for the API was negative in the Ames assay, mouse lymphoma assay, and in vivo rat micronucleus test.”

“Long-term animal studies have not been performed to evaluate the carcinogenic potential of remimazolam.”

“Regardless of these adverse effects to the pregnant female, in surviving animals, remimazolam had no adverse effects on embryo-fetal development up to 30 mg/kg/day in rat”

“Remimazolam produced typical benzodiazepine-related pharmacodynamic effects including sedation, respiratory depression, and cardiovascular depression.”

“Remimazolam showed no mutagenic potential in the bacterial reverse mutation assay.”

“Genetic toxicology battery for the API was negative in the Ames assay, mouse lymphoma assay, and in vivo rat micronucleus test.”

“Remimazolam did not induce micronuclei in the rat. In the comet assay, there was no increase of %Tail DNA up to the maximum dose.”

“Remimazolam was not investigated in a carcinogenicity study.”

“Carcinogenicity studies were not conducted or required to support the safety of the proposed acute indication with remimazolam.”

“estimated IC25 and IC50 values for remimazolam inhibition of hERG tail current were 62 and 207 μM, respectively, concentrations well above those required to activate GABAA receptors in vitro (0.36-1.38 μM) or free plasma levels reached in clinical studies.”