Abecma
idecabtagene vicleucel · BCMA CAR-TNo relevant species; NSG mouse xenografts and in vitro only
Tregzi: which tox species, and why?
allogeneic Treg immunotherapy with HSPC and T cells (Orca-T) · Allogeneic Treg + HSPC + Tcon
Species
No tox species; sublethally irradiated immunodeficient mice (xenogeneic GVHD proof-of-concept) plus published murine literature
“In the applicant’s POC studies using xenogeneic models, co-administration of human donor Tregs with Tcons demonstrated dose-dependent GVHD inhibition in sub-lethally irradiated immunodeficient mice.”
Why that species
Immunodeficient mice allow human Tcon-induced xenogeneic GVHD and Treg mitigation; no relevant tox species stated
“evaluating the ability of human Tcons to induce xenogeneic GVHD”
Surrogate molecule
Yes: published murine HSC, Treg, Tcon studies used as mechanism-of-action support; human cells tested in mouse xenograft
“Instead, in Module 4 of the BLA, the applicant submitted 45 publications delineating the MOAs of HSCs (mouse and human), Tregs (mouse), Tcons (mouse), and their combinations (mouse).”
Species: general tox
None; no toxicology studies
“No toxicology studies were conducted for TREGZI.”
Species: DART
Not conducted; not warranted based on product characteristics, biological activity and safety profile
“No genotoxicity, carcinogenicity, and developmental and reproductive toxicity (DART) studies were conducted for TREGZI. These studies are not warranted based on the product characteristics, biological activity, and safety profile.”
Species: carcinogenicity
Not conducted; not warranted
“No genotoxicity, carcinogenicity, and developmental and reproductive toxicity (DART) studies were conducted for TREGZI. These studies are not warranted based on the product characteristics, biological activity, and safety profile.”
Surrogate used in
Published murine HSC, Treg and Tcon studies (45 publications) supported mechanisms of action
“Instead, in Module 4 of the BLA, the applicant submitted 45 publications delineating the MOAs of HSCs (mouse and human), Tregs (mouse), Tcons (mouse), and their combinations (mouse).”
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
Aucatzyl
obecabtagene autoleucel · CD19 CAR-TNo relevant species; no in vivo tox. NSG xenograft (pharmacology) and human tissue cross-reactivity 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
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