Breyanzi: which tox species, and why?

“In particular, suitable animal models are not available for accurately assessing the non-clinical characteristics of a human cell-based product such as JCAR017.”

“The results support that JCAR017 is specific for human CD-19 binding and lacks species cross-reactivity, in particular towards mouse and non-human primate.”

“The lack of conventional in vivo studies and the use of immune-deficient Raji Burkitt’s lymphoma-bearing NOD/SCID IL-2Rγnull mice model are justified and appropriate to investigate autologous cell-based products.”

“In this light, traditional toxicity, including single and repeat-dose toxicity, genotoxicity, carcinogenicity, reproductive and developmental toxicity, and local tolerance studies were deemed of negligible utility and thus were not conducted.”

“JCAR017 does not survive in immunocompetent rodents and induces graft-versus-host disease in immunocompromised mice; therefore, traditional DART studies were not conducted.”

“Consistent with regulatory guidance under “Nonclinical Evaluation for Anticancer Pharmaceuticals” (ICH S9, 2009) carcinogenicity studies were not conducted.”

“The lack of conventional in vivo studies and the use of immune-deficient Raji Burkitt’s lymphoma-bearing NOD/SCID IL-2Rγnull mice model are justified and appropriate to investigate autologous cell-based products.”