Alofisel
darvadstrocel · Allogeneic adipose MSCNot conducted; cell-based product does not interact with DNA
Abecma: genotox, carcinogenicity and repro: done or skipped?
idecabtagene vicleucel · BCMA CAR-T
Genotoxicity
Not conducted (traditional); insertion site analysis of 20 clinical lots
“No traditional genotoxicity assays and carcinogenicity assessments were performed for bb2121.”
Carcinogenicity
Not conducted; in vitro IL-2-independent growth assay showed no transformation
“No carcinogenicity or tumorigenicity studies were conducted for bb2121. However, the applicant evaluated IL-2 independent growth in Study #10.”
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
In vitro expansion studies (5 patient, 2 healthy donor lots) showed no transformation; insertion site analysis on products from 20 patients
“In vitro expansion studies with CAR-positive T cells (ABECMA) from five patients and two healthy donor drug product lots showed no evidence for transformation and/or immortalization of T cells. A genomic insertion site analysis of the lentiviral vector was performed on ABECMA samples from twenty (20) individual patient donors.”
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)
“No animal reproductive and developmental toxicity studies were conducted for bb2121 which is acceptable based on the product characteristics.”
Safety pharmacology
Not conducted
“No safety pharmacology studies were conducted.”
Genotox: Ames
Not conducted (autologous human cell product)
“Ide-cel is an autologous human cellular product and therefore, standard genotoxicity studies eg, Ames assay, clastogenicity assessments were not conducted.”
Genotox: in vitro mammalian
Not conducted; vector integration site analysis of 20 clinical lots showed no preferential integration near oncogenes
“Integration site analysis was performed for 20 clinical drug product lots. The resulting data showed that the lentiviral vector does not preferentially integrate in or near genes of concern for oncogenic transformation and is consistent with other similar vectors.”
Genotox: in vivo
Not conducted (autologous human cell product)
“Ide-cel is an autologous human cellular product and therefore, standard genotoxicity studies eg, Ames assay, clastogenicity assessments were not conducted.”
Carcinogenicity model
Not conducted; in vitro IL-2-independent growth assay (5 patient, 2 healthy donors) showed no uncontrolled proliferation
“Additionally, an IL-2-independent growth assay of ABECMA® generated from five patient donors and two healthy donors showed no signs of uncontrolled cellular proliferation.”
Carcinogenicity timing
Not required; conventional animal studies not appropriate (autologous human T cells do not engraft in immunocompetent animals)
“Conventional animal studies employing common toxicology study designs are not appropriate for ide-cel since autologous human T cells do not graft in immunocompetent animals and thus, in vivo nonclinical general safety, genotoxicity, carcinogenicity, developmental safety or reproductive safety studies were not conducted.”
hERG / QT
Not conducted (no safety pharmacology studies)
“No safety pharmacology studies were conducted.”
Same question, other cell therapies
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
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