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

“CAB was negative for mutagenesis and clastogenicity in the in vitro bacterial reverse mutation assay and the in vivo micronucleus assay in rats.”

“CAB has demonstrated a lack of carcinogenic potential in conventional oral 2-year studies in mouse and rats at doses corresponding 7 and 19-fold the clinical AUC exposure in patients.”

“In the pivotal rat PPND study, an increase in the number of F1 stillbirths and early postnatal deaths by PND 4 was observed at 1,000 mg/kg/dose (27.9× higher than human exposure at the proposed human dose).”

“An IC50 was not identified in the hERG assay. Increases in heart rate and mean arterial pressure were observed at 1,000 mg/kg up to 2 hours postdose in the cardiovascular function study, but no drug-related effects on these parameters were observed in the general toxicology studies up to the highest doses tested.”