Abecma
idecabtagene vicleucel · BCMA CAR-TCountry not stated; first-in-human dose-finding study in patients with relapsed/refractory multiple myeloma (CRB-401)
StrataGraft: what was done before first-in-human, and what came after?
allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen · Allogeneic keratinocytes + fibroblasts
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 StrataGraft 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; no local or systemic toxicity to 140 days; wound site showed normal healing (FDA pharmacology/toxicology review, p. 9)
Longest repeat-dose systemic studies
Longest repeat-dose study and recovery
No repeat-dose study: single topical application in nude mice, followed to 140 days
“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.”
Pivotal GLP studies
Non-GLP 8+ week subchronic study NCREP.001 in 26 nude mice, single topical application, sacrificed to 140 days; retrospective tumorigenicity analyses to 421 days
“Minimum Eight Week Transdermal Subchronic Toxicity Study with STRATAGRAFT® Skin Tissue in Nude Mice”
DART package
Species: DART
Not conducted; acceptable given product characteristics and safety profile
“No animal reproductive or developmental toxicity (DART) studies were conducted with STRATAGRAFT, which is acceptable, considering the product characteristics and safety profile.”
Reproductive & developmental
Not conducted
“No DART studies were conducted.”
PPND / ePPND: when
No DART studies conducted; acceptable given product characteristics and safety profile
“No animal reproductive or developmental toxicity (DART) studies were conducted with STRATAGRAFT, which is acceptable, considering the product characteristics and safety profile.”
Carcinogenicity
Species: carcinogenicity
No carcinogenicity study; tumorigenicity in immunodeficient mice (topical construct 20 weeks; s.c. NIKS keratinocytes 23 weeks)
“No tumor formation was observed for the 20-week study duration. In addition, following a single subcutaneous injection of NIKS® keratinocytes in immunodeficient mice, no tumor formation was detected for the 23-week study duration.”
Carcinogenicity model
Tumorigenicity only: topical StrataGraft on immunodeficient mouse wounds 20 weeks and s.c. NIKS keratinocytes 23 weeks; no tumors
“No tumor formation was observed for the 20-week study duration. In addition, following a single subcutaneous injection of NIKS® keratinocytes in immunodeficient mice, no tumor formation was detected for the 23-week study duration.”
Carcinogenicity timing
No standard carcinogenicity study; immunodeficient-mouse tumorigenicity studies (20-week topical, 23-week s.c. NIKS cells) completed before the marketing application, no tumors
“No tumor formation was observed for the 20-week study duration. In addition, following a single subcutaneous injection of NIKS keratinocytes in immunodeficient mice, no tumor formation was detected for the 23-week study duration.”
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