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

“Zoliflodacin was not genotoxic in the mouse lymphoma assay (MLA) and rat in vivo micronucleus assay. In the Ames bacterial reverse mutation assay, zoliflodacin was mutagenic in the TA102 strain, consistent with its pharmacologic action as a bacterial topoisomerase II inhibitor.”

“Carcinogenicity studies have not been conducted with zoliflodacin.”

“In the mouse EFD study, exencephaly, a neural tube malformation, was present in litters in the 500 and 1000 mg/kg/day groups at levels above current and historical control rates.”

“In a safety pharmacology study in dogs, an oral 4-week repeat dose toxicity study in dogs, and an intravenous (IV) study in anesthetized guinea pigs, other reported cardiac effects included decreased blood pressure, increased heart rate, increase in cardiac contractility, and decreased cardiac relaxation. No arrhythmias or adverse QTc prolongation were detected in the IV-infusion safety pharmacology study in dogs.”