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

“Although maribavir demonstrated mutagenic potential in the absence of metabolic activation in the mouse lymphoma assay, given the negative results of the in vivo rat micronucleus assay and the negative bacterial mutation assay, the weight of evidence indicates that maribavir does not exhibit genotoxic potential.”

“Maribavir was not carcinogenic in rats at any dose tested, corresponding to maribavir exposures less than human exposure at the RHD. At 150 mg/kg/day in male mice only, an increased incidence of hemangiosarcoma and combined hemangioma/ hemangiosarcoma was observed across multiple tissues at exposures less than the human exposure at the RHD.”

“A decrease in the number of viable fetuses, and increase in early resorptions and post-implantation losses were observed at ≥100 mg/kg/day (at exposures approximately half the human exposure at the RHD).”

“Maribavir had no effect on the hERG current at concentrations of up to 1500 µg/mL (measured concentration 1250 µg/mL), providing a wide safety margin of more than 4000-fold the anticipated clinical plasma unbound Cmax of 0.344 µg/mL (0.91 µM), at the maximum proposed clinical dose of 400 mg BID.”