Abecma
idecabtagene vicleucel · BCMA CAR-TNot conducted (traditional); insertion site analysis of 20 clinical lots
Tecartus: genotox, carcinogenicity and repro: done or skipped?
brexucabtagene autoleucel · CD19 CAR-T
Genotoxicity
Not conducted (traditional); vector integration site analysis performed instead
“Traditional genotoxicity studies were not conducted using KTE-X19, however, given the use of a murine γ-retroviral vector to stably integrate the anti-CD19 CAR into the T cell genome, a risk associated with insertional mutagenesis exists.”
Carcinogenicity
Not conducted
“No carcinogencity/tumorigenicity studies were conducted.”
Instead of carcinogenicity
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Instead of genotoxicity
Integration site analysis using axicabtagene ciloleucel, plus published literature and ZUMA-2 clinical data
“In addition to an updated discussion of published literature and clinical trial ZUMA-2, the applicant provided summary data from an updated integration analyses conducted using axicabtagene ciloleucel (Module 4.2.3.3.2).”
DRG histopathology
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Reproductive & developmental
Not conducted (product characteristics, safety profile)
“No animal reproductive and developmental toxicity studies were conducted with KTE-X19, which is acceptable based on the product characteristics and safety profile.”
Safety pharmacology
Not conducted
“No secondary pharmacodynamics studies, safety pharmacology studies and pharmacodynamic drug interaction studies were conducted.”
Genotox: Ames
Not conducted; insertional mutagenesis risk noted from γ-retroviral vector integration
“Traditional genotoxicity studies were not conducted using KTE-X19, however, given the use of a murine γ-retroviral vector to stably integrate the anti-CD19 CAR into the T cell genome, a risk associated with insertional mutagenesis exists.”
Genotox: in vitro mammalian
Not conducted
“Traditional genotoxicity studies were not conducted using KTE-X19, however, given the use of a murine γ-retroviral vector to stably integrate the anti-CD19 CAR into the T cell genome, a risk associated with insertional mutagenesis exists.”
Genotox: in vivo
Not conducted
“Traditional genotoxicity studies were not conducted using KTE-X19, however, given the use of a murine γ-retroviral vector to stably integrate the anti-CD19 CAR into the T cell genome, a risk associated with insertional mutagenesis exists.”
Carcinogenicity model
Not conducted; acceptable based on product characteristics, safety profile and indication
“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.”
Carcinogenicity timing
Not required (acceptable based on product characteristics, safety profile and indication)
“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.”
hERG / QT
Not conducted (no safety pharmacology studies)
“No safety pharmacology studies were conducted.”
Same question, other cell therapies
Alofisel
darvadstrocel · Allogeneic adipose MSCNot conducted; cell-based product does not interact with DNA
Amtagvi
lifileucel · TIL therapyNot conducted (not warranted given product characteristics and biological activity)
Aucatzyl
obecabtagene autoleucel · CD19 CAR-TNot conducted (third-generation SIN lentiviral vector, release criterion, long-term clinical monitoring for insertional mutagenesis)
Breyanzi
lisocabtagene maraleucel · CD19 CAR-TNot conducted (traditional); lentiviral integration site mapping instead
Carvykti
ciltacabtagene autoleucel · BCMA CAR-TNot conducted (classical); lentiviral integration site analysis instead
ChondroCelect
characterised viable autologous cartilage cells · Autologous chondrocytesNot conducted (per cell-based product guideline)
Ebvallo
tabelecleucel · EBV-specific allogeneic T cellsNot conducted (ICH S6(R1)); non-genetically engineered cells
Encelto
revakinagene taroretcel · CNTF (encapsulated RPE cell implant)Done: ISO-10993 battery (bacterial, mammalian cell, mouse micronucleus on device extracts), negative
Gintuit
allogeneic cultured keratinocytes and fibroblasts in bovine collagen · Allogeneic keratinocytes + fibroblastsNot conducted (nature of product and clinical experience)
Holoclar
autologous corneal epithelial cells containing limbal stem cells · Autologous limbal stem cellsNot conducted (classical); in vitro karyotype analysis of cells
Kymriah
tisagenlecleucel · CD19 CAR-TNot conducted (classical); lentiviral integration site analysis on 14 donor products
Lantidra
donislecel · Allogeneic pancreatic isletsNot conducted
Laviv
azficel-T · Autologous fibroblastsNot conducted (autologous nature, prior human experience)
MACI
autologous cultured chondrocytes on porcine collagen membrane · Autologous chondrocytesNot conducted on cells; four studies on collagen membrane were non-mutagenic
Omisirge
omidubicel · Expanded cord blood HPCNo standard genotox; cytogenetic/karyotype analyses of CF and NF showed no clonal aneuploidy
Provenge
sipuleucel-T · PAP-GM-CSF (autologous APC)Not conducted (autologous nature of product)
Rethymic
allogeneic processed thymus tissue · Allogeneic thymus tissueNot conducted
Ryoncil
remestemcel-L · Allogeneic BM-MSCNot conducted (not warranted)
Spherox
spheroids of autologous matrix-associated chondrocytes · Autologous chondrocyte spheroidsNot conducted (per cell-based product guideline)
StrataGraft
allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen · Allogeneic keratinocytes + fibroblastsNot conducted
Tecelra
afamitresgene autoleucel · MAGE-A4 TCR-TNot conducted (no test models or relevant species); integration site analysis showed polyclonal products, no selective insertion
Tregzi
allogeneic Treg immunotherapy with HSPC and T cells (Orca-T) · Allogeneic Treg + HSPC + TconNot conducted
Yescarta
axicabtagene ciloleucel · CD19 CAR-TNot conducted; literature review of retroviral-transduced T-cell transformation risk instead
Zalmoxis
allogeneic T cells modified with HSV-TK / dLNGFR (nalotimagene carmaleucel) · HSV-TK suicide-gene T cellsNot conducted; in vitro retroviral integration site analysis instead
Zemcelpro
dorocubicel · UM171-expanded cord blood CD34+Done for residual UM171 only (Ames, CHO micronucleus negative) plus cytogenetics of treated cells; none for cells