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

“Zanubrutinib was not mutagenic in the in vitro bacterial reverse mutation test or clastogenic in either the in vitro chromosomal aberrations assay or in the in vivo bone marrow micronucleus assay in rats.”

“No carcinogenicity studies have been conducted or are required to support marketing of zanubrutinib for the current indication.”

“In an embryo-fetal development study in female rats, once daily administration of zanubrutinib at 30, 75, or 150 mg/kg/day on GD 6-17 resulted in fetal heart malformations in the form of 2- or 3-chambered hearts.”

“Zanubrutinib had no toxicologically-significant effects on cardiovascular function in a cardiovascular study in telemetered dogs, and had no effects on neurobehavioral function, temperature, or respiratory function in CNS and respiratory studies conducted in male rats.”