Veklury: which tox species, and why?

“Repeat-dose toxicity in rats and cynomolgus monkeys have been conducted, 2-week studies with a 4-week recovery period, and 4-week studies in both species.”

“Pharmacokinetic studies supported the selection of the rat and monkey for the assessment of RDV toxicology. Both rat and monkey formed the intermediate metabolite GS-704277 and the nucleoside metabolite GS-441524.”

“Intravenous administration (slow bolus) of remdesivir to rats at dosage levels of ≥3 mg/kg/day for up to 4 weeks resulted in findings indicative of kidney injury and/or dysfunction.”

“repeat-dose toxicology studies in rats and Cynomolgus macaques for up to a month; two follow-up 1-week toxicology studies in Cynomolgus and Rhesus macaques”

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

“Nonclinical in vivo studies were in general performed with a formulation of remdesivir in 12% (w/v) sulfobutylether B-cyclodextrin sodium (SBECD) in sterile water for injection, pH 3.5 +/-0.1, which is representative of the clinical formulations.”