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

“Traditional genotoxicity assays and carcinogenicity assessments were not performed for JCAR017.”

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

“Lentiviral integration sites were characterized to evaluate the risk for insertional toxicities in the JCAR017. An unbiased, genome-wide, assay assessed viral integration events across 54 CAR T cell products derived from 34 patients that were transduced with vector to produce JCAR017.”

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

“The autologous cell-based JCAR017 T products lack species cross-reactivity thus in all NC studies performed safety pharmacology was deemed not practical and of negligible utility.”

“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.”

“An unbiased, genome-wide, assay assessed viral integration events across 54 CAR T cell products derived from 34 patients that were transduced with vector to produce JCAR017.”

“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.”

“An in vitro GLP-compliant study evaluated the IL-2 independent growth of JCAR017 to assess the risk of oncogenic transformation following transduction.”

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

“No safety pharmacology studies were conducted.”