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

“Remdesivir was not genotoxic in a battery of assays, including bacterial mutagenicity, chromosome aberration using human peripheral blood lymphocytes, and in vivo rat micronucleus assays.”

“Given the short-term administration of VEKLURY for the treatment of COVID-19, long-term animal studies to evaluate the carcinogenic potential of remdesivir were not conducted.”

“In the reproductive and development toxicity studies, there was a decrease in corpora lutea, a consequent decrease in implantation sites and viable embryos, and lower ovary and uterus/cervix/oviduct weights in the rats at 10 mg/kg; these changes were observed at a systemically toxic dose. There were no remarkable findings in male rats in the fertility study, no adverse findings in embryo-fetal studies in rats and rabbits, and no adverse changes in the pre- and postnatal study in rats.”

“RDV did show only a weak inhibition in vitro of the hERG channel, IC20 and IC50 values for the inhibitory effect were 7.5 μM and 28.9 μM, respectively”

“RDV and metabolite GS-441524 were negative in in vitro Ames tests.”

“In a chromosome aberration assay in human peripheral blood lymphocytes RDV showed an equivocal response after metabolic activation and was negative without metabolic activation.”

“In an in vivo micronucleus test performed in rats, RDV was negative up to doses of 50 mg/kg/d at GS-441524 exposures of about an order of magnitude higher than the anticipated human exposure.”

“RDV is indicated for short-term use only, no carcinogenicity studies have been performed. This is agreed upon.”

“RDV is indicated for short-term use only, no carcinogenicity studies have been performed. This is agreed upon.”

“RDV did show only a weak inhibition in vitro of the hERG channel, IC20 and IC50 values for the inhibitory effect were 7.5 μM and 28.9 μM, respectively; at least 6-fold and 26-fold, respectively, above the estimated free drug concentration (1.1 μM) at Cmax of the currently proposed 200-mg maximum clinical dose.”