Abecma
idecabtagene vicleucel · BCMA CAR-TNo relevant species; NSG mouse xenografts and in vitro only
Aucatzyl: which tox species, and why?
obecabtagene autoleucel · CD19 CAR-T
Species
No relevant species; no in vivo tox. NSG xenograft (pharmacology) and human tissue cross-reactivity only
“Per the applicant, conventional nonclinical toxicology studies were not conducted because they do not yield clinically relevant information for a CAR T cell product.”
Why that species
No pharmacologically responsive species; human autologous T cells will not engraft in immunocompetent animals; immunodeficient models uninformative
“Aucatzyl, a patient-specific product, is not appropriate for administration to immunocompetent animals, as the T cells will not engraft.”
Surrogate molecule
No surrogate; nonclinical CAT19 CAR T cells from healthy-donor PBMCs with identical construct judged representative
“Despite minor differences between the nonclinical and clinical products, the constructs assessed, including the binding domain, were identical and therefore the nonclinical product is considered appropriate to assess safety and activity in the nonclinical program.”
Species: general tox
None; general toxicity studies not conducted (no pharmacologically responsive species)
“The absence of general toxicity studies is accepted, considering that there are no pharmacologically responsive animal species (as also mentioned in the scientific advice, EMA/CHMP/SAWP/586752/2019).”
Species: DART
Not conducted (ICH S9; no pharmacologically relevant species)
“DART studies are not needed for indications falling under ICH S9 scope (advanced cancer) and no pharmacologically relevant animal species is available.”
Species: carcinogenicity
Not conducted (ICH S9; no cross-reactivity with murine CD19)
“Carcinogenicity studies are not needed for indications falling under ICH S9 scope (advanced cancer). In addition, there is no cross-reactivity of the CD19-CAR T cells from Aucatzyl with the murine antigen.”
Surrogate used in
No surrogate used; nonclinical CAT19 CAR T cells with identical construct judged representative
“Despite minor differences between the nonclinical and clinical products, the constructs assessed, including the binding domain, were identical and therefore the nonclinical product is considered appropriate to assess safety and activity in the nonclinical program.”
Same question, other cell therapies
Alofisel
darvadstrocel · Allogeneic adipose MSCImmunocompromised athymic nude rats (GLP); nude mice for tumourigenicity
Amtagvi
lifileucel · TIL therapyNo animal studies with product; published murine and human TIL literature only
Breyanzi
lisocabtagene maraleucel · CD19 CAR-TNo relevant species; in vitro and NSG mouse xenograft only
Carvykti
ciltacabtagene autoleucel · BCMA CAR-TNo relevant species; NCG mouse xenografts, non-GLP NHP pilot with autologous NHP CAR-T
ChondroCelect
characterised viable autologous cartilage cells · Autologous chondrocytesNude mouse (ectopic), sheep and goat (orthotopic); non-GLP combined PD/PK/tox
Ebvallo
tabelecleucel · EBV-specific allogeneic T cellsSCID mice (EBV+ lymphoma xenograft, literature/PD); no tox species
Encelto
revakinagene taroretcel · CNTF (encapsulated RPE cell implant)Minipig, pig and rabbit (ocular tox/PK); rcd1 dog for pharmacology; rat and rabbit for rhCNTF DART
Gintuit
allogeneic cultured keratinocytes and fibroblasts in bovine collagen · Allogeneic keratinocytes + fibroblastsAthymic (nude) mice for pharmacology; rabbits, guinea pigs, mice for biocompatibility
Holoclar
autologous corneal epithelial cells containing limbal stem cells · Autologous limbal stem cellsNo animal species; abridged programme of in vitro tumorigenicity assays and literature
Kymriah
tisagenlecleucel · CD19 CAR-TNo relevant species; immunodeficient mouse B-ALL xenograft (non-GLP) only
Lantidra
donislecel · Allogeneic pancreatic isletsNo studies with product; literature only (diabetic mice, rats, NHP, pigs)
Laviv
azficel-T · Autologous fibroblastsNo preclinical or toxicology studies conducted with the product
MACI
autologous cultured chondrocytes on porcine collagen membrane · Autologous chondrocytesRabbit and horse, with analogous MACI (species-matched autologous cells on ACI-Maix)
Omisirge
omidubicel · Expanded cord blood HPCImmunodeficient irradiated NOD/SCID mouse only (xenogeneic human cells)
Provenge
sipuleucel-T · PAP-GM-CSF (autologous APC)No conventional tox species; rat and mouse proof-of-concept studies with rodent surrogate products
Rethymic
allogeneic processed thymus tissue · Allogeneic thymus tissueNo relevant species; nude rat pharmacology studies only, no tox
Ryoncil
remestemcel-L · Allogeneic BM-MSCRat, baboon and pig using species-specific surrogate ceMSC
Spherox
spheroids of autologous matrix-associated chondrocytes · Autologous chondrocyte spheroidsImmunodeficient (SCID/NSG) mice, Goettingen minipig, Merino sheep; no conventional tox
StrataGraft
allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen · Allogeneic keratinocytes + fibroblastsAthymic nude mice only (immunodeficient wound model)
Tecartus
brexucabtagene autoleucel · CD19 CAR-TNo relevant species; in vitro and syngeneic mouse surrogate CAR-T only
Tecelra
afamitresgene autoleucel · MAGE-A4 TCR-TNo relevant species; in vitro cross-reactivity/alloreactivity and murine xenograft pharmacology only
Tregzi
allogeneic Treg immunotherapy with HSPC and T cells (Orca-T) · Allogeneic Treg + HSPC + TconNo tox species; sublethally irradiated immunodeficient mice (xenogeneic GVHD proof-of-concept) plus published murine literature
Yescarta
axicabtagene ciloleucel · CD19 CAR-TNo relevant species; syngeneic mouse lymphoma model with murine surrogate CAR-T (published, non-GLP)
Zalmoxis
allogeneic T cells modified with HSV-TK / dLNGFR (nalotimagene carmaleucel) · HSV-TK suicide-gene T cellsImmunodeficient NOD/SCID mice (GvHD xenograft models); no conventional tox species
Zemcelpro
dorocubicel · UM171-expanded cord blood CD34+Female sub-lethally irradiated NSG mice (human cells); UM171 compound PK/tox in NSG mouse, rat, cynomolgus monkey