Abecma
idecabtagene vicleucel · BCMA CAR-TNot conducted (traditional); insertion site analysis of 20 clinical lots
Laviv: genotox, carcinogenicity and repro: done or skipped?
azficel-T · Autologous fibroblasts
Genotoxicity
Not conducted (autologous nature, prior human experience)
“were not conducted by the sponsor due to the autologous nature of IT and the previous human experience.”
Carcinogenicity
Not conducted (autologous, minimally manipulated); tumorigenicity listed as a gap
“were not conducted by the sponsor due to the autologous nature of IT and the previous human experience.”
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
Not applicable: cells not genetically modified
“were not conducted by the sponsor due to the autologous nature of IT and the previous human experience.”
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 (autologous nature, prior human experience)
“were not conducted by the sponsor due to the autologous nature of IT and the previous human experience.”
Safety pharmacology
Not conducted (autologous nature, prior human experience)
“were not conducted by the sponsor due to the autologous nature of IT and the previous human experience.”
Genotox: Ames
Not conducted (autologous product, prior human experience)
“Toxicology studies as described in the International Conference on Harmonisation (ICH) Safety (‘S’) guidelines, consisting of pharmacokinetics, acute toxicology, chronic toxicology, genotoxicity, carcinogenicity, reproductive and developmental toxicity, safety pharmacology, and immunotoxicity (http://www.ich.org/cache/compo/276-254- 1.html) were not conducted by the sponsor due to the autologous nature of IT and the previous human experience.”
Genotox: in vitro mammalian
Not conducted (autologous product, prior human experience)
“Toxicology studies as described in the International Conference on Harmonisation (ICH) Safety (‘S’) guidelines, consisting of pharmacokinetics, acute toxicology, chronic toxicology, genotoxicity, carcinogenicity, reproductive and developmental toxicity, safety pharmacology, and immunotoxicity (http://www.ich.org/cache/compo/276-254- 1.html) were not conducted by the sponsor due to the autologous nature of IT and the previous human experience.”
Genotox: in vivo
Not conducted (autologous product, prior human experience)
“Toxicology studies as described in the International Conference on Harmonisation (ICH) Safety (‘S’) guidelines, consisting of pharmacokinetics, acute toxicology, chronic toxicology, genotoxicity, carcinogenicity, reproductive and developmental toxicity, safety pharmacology, and immunotoxicity (http://www.ich.org/cache/compo/276-254- 1.html) were not conducted by the sponsor due to the autologous nature of IT and the previous human experience.”
Carcinogenicity model
Not conducted; published nude-mouse study (two animals, 2 months) inconclusive for tumorigenicity
“Regarding the in vivo assessment of tumorigenic potential: 1) only two animals were used and 2) the study duration was only 2 months, therefore no conclusions can be made about this safety endpoint.”
Carcinogenicity timing
Not required: autologous, minimally manipulated cells judged unlikely to become tumorigenic
“The pharmacology/toxicology review of the original IND submission supported the sponsor’s decision, noting that these cells are autologous, minimally manipulated, highly unlikely to change in phenotype, dedifferentiate, migrate or become tumorigenic (see Attachment I).”
hERG / QT
Not conducted (no safety pharmacology studies)
“Toxicology studies as described in the International Conference on Harmonisation (ICH) Safety (‘S’) guidelines, consisting of pharmacokinetics, acute toxicology, chronic toxicology, genotoxicity, carcinogenicity, reproductive and developmental toxicity, safety pharmacology, and immunotoxicity (http://www.ich.org/cache/compo/276-254- 1.html) were not conducted by the sponsor due to the autologous nature of IT and the previous human experience.”
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
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
Tecartus
brexucabtagene autoleucel · CD19 CAR-TNot conducted (traditional); vector integration site analysis performed instead
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