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Precedia/Cell therapy/StrataGraft/Flexibility

StrataGraft: what flexibility did regulators accept, and why?

allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen · Allogeneic keratinocytes + fibroblasts
Check my plan vs. these
Flexibility accepted
OtherCriticised but acceptedBeyond the letter
Toxicity assessed only in immunodeficient mice, with significant study design and data limitations
Why: Human cells would elicit a xenogeneic response in immune-competent animals · No relevant species
“Reviewer’s Conclusion: Within the significant limitations of the study design and data provided, no apparent local or systemic toxicity was observed out to 140 days following topical application of STRATAGRAFT® to immunodeficient mice with an existing wound.”
✓ VerifiedFDA pharmacology/toxicology review, p. 10Source ↗
“Note: STRATAGRAFT® is composed of human cells, thus the potential for elicitation of a xenogeneic response following administration in immune competent animals exists.”
✓ VerifiedFDA pharmacology/toxicology review, p. 6Source ↗
Efficacy modelVerdict not stated
No nonclinical pharmacology studies; claimed wound-healing mechanisms deferred to clinical data
“However, no nonclinical pharmacology studies were conducted; please refer to the clinical review memo for confirmation of these claims.”
✓ VerifiedFDA pharmacology/toxicology review, p. 5Source ↗
BiodistributionVerdict not stated
No pharmacokinetic or cell distribution studies; persistence assessed in three completed clinical trials
Why: Persistence evaluated in three completed clinical trials · Human data
“No PK studies were conducted. The applicant refers to the three completed clinical trials: STRATA2011, STRATA2014, and STRATA2016.”
✓ VerifiedFDA pharmacology/toxicology review, p. 5Source ↗
DARTAcceptedBeyond the letter
No reproductive or developmental toxicity studies
Why: Product characteristics and safety profile · Low-risk modality
“No animal reproductive or developmental toxicity (DART) studies were conducted with STRATAGRAFT, which is acceptable, considering the product characteristics and safety profile.”
✓ VerifiedFDA summary basis for approval, p. 12Source ↗

Same question, other cell therapies

Abecma

idecabtagene vicleucel · BCMA CAR-T
No single or repeat-dose in vivo toxicity studies; no appropriate animal model for autologous human CAR-T cells

Alofisel

darvadstrocel · Allogeneic adipose MSC
No reproductive and developmental toxicity studies

Amtagvi

lifileucel · TIL therapy
No nonclinical pharmacology studies with the product; published data on similar murine and human tumor-derived T lymphocytes cited instead

Aucatzyl

obecabtagene autoleucel · CD19 CAR-T
No general toxicity studies; no pharmacologically relevant species for human CAR T cells

Breyanzi

lisocabtagene maraleucel · CD19 CAR-T
No pharmacologically relevant species; no conventional single- or repeat-dose toxicity, local tolerance or other traditional studies

Carvykti

ciltacabtagene autoleucel · BCMA CAR-T
No GLP-compliant formal toxicology studies and no repeat-dose study; no relevant animal species

ChondroCelect

characterised viable autologous cartilage cells · Autologous chondrocytes
All nonclinical studies non-GLP, run as combined pharmacodynamic/distribution/toxicity studies in nude mice, sheep and goats

Ebvallo

tabelecleucel · EBV-specific allogeneic T cells
No single- or repeat-dose toxicity studies; no relevant animal model for an HLA-restricted human T-cell product

Encelto

revakinagene taroretcel · CNTF (encapsulated RPE cell implant)
No carcinogenicity/tumorigenicity studies; waived on toxicological risk assessments of rhCNTF and residual medium

Gintuit

allogeneic cultured keratinocytes and fibroblasts in bovine collagen · Allogeneic keratinocytes + fibroblasts
ICH toxicology package (chronic toxicity, genotoxicity, carcinogenicity, DART, safety pharmacology, immunotoxicity) not conducted; partly covered by device biocompatibility testing

Holoclar

autologous corneal epithelial cells containing limbal stem cells · Autologous limbal stem cells
No in vivo toxicity studies (single dose, repeat dose, immunogenicity); no suitable animal model

Kymriah

tisagenlecleucel · CD19 CAR-T
No single-dose or standard toxicity studies: patient-specific human cell product cannot be given to immunocompetent animals

Lantidra

donislecel · Allogeneic pancreatic islets
No nonclinical studies with the product; published islet-transplant literature in rodents and monkeys relied on instead

Laviv

azficel-T · Autologous fibroblasts
No preclinical studies of any kind with the product; relied on prior commercial human use and published literature

MACI

autologous cultured chondrocytes on porcine collagen membrane · Autologous chondrocytes
No carcinogenicity/tumorigenicity studies

Omisirge

omidubicel · Expanded cord blood HPC
In vivo studies described as GLP lacked QA statements, facility information and deviation reports

Provenge

sipuleucel-T · PAP-GM-CSF (autologous APC)
No conventional toxicology or pharmacokinetic studies; risk-based approach justification instead

Rethymic

allogeneic processed thymus tissue · Allogeneic thymus tissue
No nonclinical toxicology studies: no relevant animal species or model

Ryoncil

remestemcel-L · Allogeneic BM-MSC
Nonclinical studies used surrogate animal-derived MSC and human MSC from an early manufacturing process, not the commercial product

Spherox

spheroids of autologous matrix-associated chondrocytes · Autologous chondrocyte spheroids
No long-term toxicity data: pivotal 9-month GLP sheep study failed through loss of the implants

Tecartus

brexucabtagene autoleucel · CD19 CAR-T
No relevant animal model; no GLP formal toxicology studies, only safety observations in a syngeneic mouse surrogate model

Tecelra

afamitresgene autoleucel · MAGE-A4 TCR-T
No in vivo single- or repeat-dose toxicity studies; no appropriate animal model for human TCR-engineered T cells

Tregzi

allogeneic Treg immunotherapy with HSPC and T cells (Orca-T) · Allogeneic Treg + HSPC + Tcon
No nonclinical toxicology studies; safety supported by clinical data with a similar cell product

Yescarta

axicabtagene ciloleucel · CD19 CAR-T
No toxicology studies with the product; no relevant animal model, murine surrogate CAR-T used for pharmacology

Zalmoxis

allogeneic T cells modified with HSV-TK / dLNGFR (nalotimagene carmaleucel) · HSV-TK suicide-gene T cells
No conventional toxicology studies; safety read from two immunodeficient-mouse GvHD pharmacology models

Zemcelpro

dorocubicel · UM171-expanded cord blood CD34+
UM171 toxicity studies in rats (single dose) and monkeys (three doses) not GLP-compliant

Summary across all 27 cell therapies →