Abecma
idecabtagene vicleucel
Species
no relevantMouse
Longest study
12 wk
Genotox
Not conducted Not conducted
Carcinogenicity
Not conducted Not conducted
Repro
Not conducted Not conducted
First dose
Partial / alternative Partly stated
Speciesopen answer page →
Species
No relevant species; NSG mouse xenografts and in vitro only
“The PK and biodistribution of ide-cel were evaluated in NSG mice with and without BCMA+ xenografts.”
Why that species
Human autologous T cells do not engraft in immunocompetent animals; no representative models
“Ide-cel comprises engineered human T cells, therefore there are no representative in vitro assays, ex vivo models, or in vivo models that can accurately address the toxicological characteristics of the human product.”
Surrogate molecule
No surrogate; human ide-cel tested in NSG mice with human MM xenografts
“Rapid elimination of both subcutaneous and systemic tumours and increased survival was demonstrated in NSG mice with BCMA+ xenografts after a single dose of ide-cel.”
Study lengthopen answer page →
Longest pivotal study
Pivotal GLP studies
None GLP; non-GLP NSG mouse PK/PD/biodistribution/general safety study (B4-15-090, single IV, 29 days)
“No single or repeat-dose toxicity studies were conducted with ide-cel as traditional animal studies employing common toxicology study designs are not appropriate for ide-cel”
Route in tox
Intravenous (tail vein, single dose)
“ide-cel was administered to mice as a single IV injection via tail vein with no abnormal observations recorded at the injection site.”
Skipped studiesopen answer page →
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.”
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.”
First doseopen answer page →
First-in-human starting dose
Not explicitly stated; mouse MED 6.16x10^5 CAR+ cells corresponds to HED 2.05x10^8 CAR+ T cells (100 kg)
“expression which represents the human equivalent dose (HED) of 2.05 x 108 CAR+ T cells for a 100-kg human.”
NOAEL / key findings
No NOAEL; no bb2121-related adverse findings in mouse studies
“No bb2121-related adverse findings were reported in these studies.”
Risksopen answer page →
Immune & cytokine safety
BCMA-specific IFN-γ release in vitro; CRS not modeled; expected depletion of normal plasma cells
“It is also expected that ide-cel will deplete healthy plasma cells that express BCMA.”
Biodistribution & persistence
NSG mice: distribution to lungs, blood, bone marrow, liver, spleen; biphasic peaks Days 2/11 blood, 8/15 tissues
“A biphasic peak expansion of bb2121 cells was observed on Days 2 and 11 in the peripheral blood and Days 8 and 15 in analyzed tissues in tumor-bearing mice.”
Modality-specific risk
Insertional mutagenesis from lentiviral integration; tumorigenic transformation
“A tailored safety evaluation was conducted which focused on the investigation of the risk of insertional mutagenesis due to lentiviral integration in the genome of ide-cel CAR T cells”