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

“Zuranolone was negative in Ames, in vitro chromosomal aberration, and rat bone marrow micronucleus assays.”

“The carcinogenic potential of zuranolone was tested in a 6-month Tg.rasH2 transgenic mouse assay and in a 2-year rat carcinogenicity study. Both studies were adequately conducted and, according to the Food and Drug Administration (FDA) statistical analyses, negative for drug-induced tumors.”

“Malformations were observed in 10 HD pups (5 litters): exencephaly (1 fetus), absent tail (2 littermates), short thread-like tail and/or malformation of the sacral and caudal vertebrae (2 littermates), umbilical hernia and depressed eye bulges (1 fetus), absent or small lens of the eye (2 littermates) and vertebral/rib malformations (2 littermates).”

“A complete battery of safety pharmacology studies (CNS, cardiovascular, respiratory, hERG channel, and cardiac ion channel assays) was conducted. In the in vitro hERG assay, the IC20 for inhibition by zuranolone was 2.43µM, which is approximately 10 times the human steady-state maximum plasma concentration (Cmax).”