Tecartus: what flexibility did regulators accept, and why?

“Toxicology Similar as the pharmacology evaluation, also the non-clinical safety evaluation of KTE-X19 has been severely limited due to the lack of a relevant animal model. Therefore, no GLP-compliant formal toxicology studies were performed.”

“There were no nonclinical deficiencies identified in this submission and no outstanding requests for additional nonclinical data.”

“Since both models do have clear, although differing, limitations with regard to the translation of the non-clinical pharmacology data to human, additional non-clinical in vivo pharmacology data (e.g. testing of KTE-X19 in immunocompromised animals transplanted with human CD19+ tumour cells) would not add significant value”

“in immunocompetent mice is an acceptable approach that overcomes some of the limitations of the in vivo testing of KTE-X19 in immunocompromised animals (e.g. unspecific xenogeneic immune responses of KTE-X19 in mice, lack of complex interactions of the CAR T cells with other components of the immune system).”

“Traditional in vitro and in vivo genotoxicity and carcinogenicity/tumorigenicity assessments of KTE-X19 were not conducted which is acceptable based on the product characteristics, safety profile and indication.”

“The lack of non-clinical reproductive and developmental toxicity studies is acceptable based on the type of product, the expression pattern of the target antigen and the lack of a relevant animal model.”