Abecma
idecabtagene vicleucel · BCMA CAR-TCountry not stated; first-in-human dose-finding study in patients with relapsed/refractory multiple myeloma (CRB-401)
Omisirge: what was done before first-in-human, and what came after?
omidubicel · Expanded cord blood HPC
Before first-in-human
First-in-human: where
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.
Repeat-dose tox before first-in-human
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.
First-in-human starting dose
Not stated in public reviews
Why it's blank
The public FDA and EMA reviews of Omisirge don't say how the first human dose was chosen. That rationale is in the IND, which is confidential, so it is missing for most approved products.
How it's usually set for cell therapies
FDA expects preclinical proof-of-concept and toxicology studies to identify active dose levels and support the choice of starting dose and escalation. The 2013 guidance gives no numeric formula or scaling rule for the starting dose.
“Selection of potential starting dose level, dose-escalation schedule, and dosing regimen for clinical trials.”
✓ VerifiedFDA 2013: Preclinical Assessment of Investigational Cellular and Gene Therapy…, p. 7Source ↗
This product's starting point
NOAEL / key findings: No NOAEL stated; no test article-related adverse effects at up to 10x10^6 CF + 5x10^6 NF cells/mouse; deaths attributed to irradiation (FDA pharmacology/toxicology review, p. 28)
Longest repeat-dose systemic studies
Longest repeat-dose study and recovery
No repeat-dose study (single IV infusion in irradiated NOD/SCID mice)
“To assess the safety of the CF + NF cells following a single intravenous infusion into irradiated NOD-SCID mice.”
Pivotal GLP studies
One GLP single-dose IV toxicity/biodistribution study in irradiated NOD/SCID mice, sacrifices Day 1, Week 4, Week 12
“The following toxicology study was conducted to evaluate the safety of the test article following administration in the NOD/SCID mouse.”
DART package
Species: DART
Not conducted; no reproductive organ findings in mouse toxicity study and conditioning regimen affects fertility
“Per the applicant, developmental and reproductive toxicology studies were not conducted because there were no test article-related toxicity findings in reproductive organs as assessed by histopathological analyses”
Reproductive & developmental
Not conducted (no reproductive organ findings; conditioning regimen already affects fertility)
“Per the applicant, developmental and reproductive toxicology studies were not conducted because there were no test article-related toxicity findings in reproductive organs as assessed by histopathological analyses”
PPND / ePPND: when
Not conducted: no reproductive organ findings in mouse toxicity study; conditioning regimen already affects fertility
“Per the applicant, developmental and reproductive toxicology studies were not conducted because there were no test article-related toxicity findings in reproductive organs as assessed by histopathological analyses”
Carcinogenicity
Species: carcinogenicity
Not conducted (not warranted based on product characteristics and safety profile)
“Carcinogenicity and developmental and reproductive toxicity studies were not conducted with omidubicel-onlv. These studies are not warranted based on the product characteristics and safety profile.”
Carcinogenicity model
Not conducted (not warranted); single-dose mouse toxicity and genetic stability data showed no tumorigenic concern
“No carcinogenicity/tumorgenicity studies were conducted with the test article and were not warranted based on the known safety profile. Genetic stability and single-dose toxicity were assessed in Study No. 10 (GAM-066-AIT-BIO) and did not reveal specific tumorigenic or oncogenic concerns.”
Carcinogenicity timing
Not required: not warranted based on product characteristics and safety profile
“No carcinogenicity or reproductive and developmental toxicity studies were conducted with OMISIRGE. These studies are not warranted based on the product characteristics and safety profile.”
Same question, other cell therapies
Carvykti
ciltacabtagene autoleucel · BCMA CAR-TCountry not stated; first clinical trial in patients with relapsed/refractory multiple myeloma (LEGEND-2)
MACI
autologous cultured chondrocytes on porcine collagen membrane · Autologous chondrocytesOutside the United States: all clinical studies ex-US (countries not named)
Tecelra
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Yescarta
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Zemcelpro
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Alofisel
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Amtagvi
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Aucatzyl
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Breyanzi
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ChondroCelect
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Ebvallo
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Encelto
revakinagene taroretcel · CNTF (encapsulated RPE cell implant)Not stated in public reviews
Gintuit
allogeneic cultured keratinocytes and fibroblasts in bovine collagen · Allogeneic keratinocytes + fibroblastsNot stated in public reviews
Holoclar
autologous corneal epithelial cells containing limbal stem cells · Autologous limbal stem cellsNot stated in public reviews
Kymriah
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Lantidra
donislecel · Allogeneic pancreatic isletsNot stated in public reviews
Laviv
azficel-T · Autologous fibroblastsNot stated in public reviews
Provenge
sipuleucel-T · PAP-GM-CSF (autologous APC)Not stated in public reviews
Rethymic
allogeneic processed thymus tissue · Allogeneic thymus tissueNot stated in public reviews
Ryoncil
remestemcel-L · Allogeneic BM-MSCNot stated in public reviews
Spherox
spheroids of autologous matrix-associated chondrocytes · Autologous chondrocyte spheroidsNot stated in public reviews
StrataGraft
allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen · Allogeneic keratinocytes + fibroblastsNot stated in public reviews
Tecartus
brexucabtagene autoleucel · CD19 CAR-TNot stated in public reviews
Tregzi
allogeneic Treg immunotherapy with HSPC and T cells (Orca-T) · Allogeneic Treg + HSPC + TconNot stated in public reviews
Zalmoxis
allogeneic T cells modified with HSV-TK / dLNGFR (nalotimagene carmaleucel) · HSV-TK suicide-gene T cellsNot stated in public reviews