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

“Rilzabrutinib was not mutagenic in an in vitro bacterial reverse mutagenicity (Ames) assay, was not clastogenic in an in vitro human peripheral lymphocyte chromosomal aberration assay, nor was it clastogenic in an in vivo bone marrow micronucleus assay in rats.”

“Rilzabrutinib was not carcinogenic in a 6-month study in Tg.rasH2 mice at doses up to 300 mg/kg/day. In a 2-year rat carcinogenicity study at doses of 10, 30 or 100 and 5, 15 or 50 mg/kg/day in males and females, respectively, there were no rilzabrutinib-related tumors.”

“However, adverse visceral and skeletal findings occurred in rat fetuses at a maternally toxic dose at exposures 22 times the human exposure (based on AUC) at the MRHD (see Animal Data).”

“The in vivo studies were conducted at doses up to 500 mg/kg, which did not show any adverse rilzabrutinib-related effects in the CNS, respiratory or cardiovascular systems (including QTc).”