Zevaskyn
prademagene zamikeracel
Species
Mouse
Longest study
8 wk
Genotox
Not conducted Not conducted
Carcinogenicity
Not conducted Not conducted
Repro
Not conducted Not conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
Mouse only (immunodeficient mice with implanted human keratinocyte products); no relevant large-animal species
“In the toxicology and biodistribution (BD) study, nonclinical products representative of ZEVASKYN comprised of human acellular dermal matrix and RVV-transduced human keratinocytes (cells alone) were implanted into excisional wounds generated in mice for 4- or 8-weeks.”
Why that species
Not stated in public reviews
Surrogate molecule
Yes: representative nonclinical product (RVV-transduced human keratinocytes on human acellular dermal matrix)
“In vivo pharmacology studies were conducted with a nonclinical product representative of ZEVASKYN comprised of vector (the RVV, or vectors similar to the RVV)-transduced human keratinocytes (cells alone or cells grown into sheets) affixed to a block of human acellular dermal matrix or dermis.”
Study lengthopen answer page →
Longest pivotal study
8 weeks
“In the toxicology and biodistribution (BD) study, nonclinical products representative of ZEVASKYN comprised of human acellular dermal matrix and RVV-transduced human keratinocytes (cells alone) were implanted into excisional wounds generated in mice for 4- or 8-weeks.”
Pivotal GLP studies
One combined toxicology/biodistribution study in mice, implantation into excisional wounds, 4- and 8-week sacrifices
“In the toxicology and biodistribution (BD) study, nonclinical products representative of ZEVASKYN comprised of human acellular dermal matrix and RVV-transduced human keratinocytes (cells alone) were implanted into excisional wounds generated in mice for 4- or 8-weeks.”
Route in tox
Implantation into excisional skin wounds (topical/cutaneous)
“Nonclinical products were then implanted into excisional wounds generated in mice.”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (integration site analysis in transduced RDEB keratinocytes instead; no clonality or oncogene preference)
“Integration site analysis (ISA) was performed on RDEB keratinocytes (n=6 donors) transduced with RVV. ISA did not indicate clonality at 6-days post-keratinocyte transduction.”
Carcinogenicity
Not conducted (no neoplastic histology, low insertional oncogenesis risk, routine SCC screening in RDEB)
“Carcinogenicity and tumorigenicity studies of ZEVASKYN were not conducted due to absence of neoplastic features on histology, low risk of insertional oncogenesis, and frequent SCC screening recommended for all subjects with RDEB.”
Reproductive & developmental
Not conducted (vector biodistribution confined to the implanted product)
“Developmental and reproductive toxicity (DART) studies of ZEVASKYN were not conducted due to the BD of RVV remaining confined to representative nonclinical products.”
Safety pharmacology
Not stated in public reviews
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
No gross or histopathological findings in any tissue, including explanted products; no NOAEL stated
“There were no gross or histopathological findings in any tissue assessed, including the explanted nonclinical products.”
Risksopen answer page →
Immune & cytokine safety
Clinical only: transient anti-Col7 antibodies in 2/7 Phase 1/2a subjects; no systemic immune responses in Phase 3
“In the Phase 1/2a study, circulating anti-Col7 antibodies were detected in two out of seven subjects, which resolved without intervention by 1 year after treatment.”
Biodistribution & persistence
COL7A1 transgene DNA confined to explanted product at 4 and 8 weeks; below detection in all other tissues
“COL7A1 transgene DNA was detected in explanted nonclinical products at both sacrifice time points.”
Modality-specific risk
Retroviral insertional oncogenesis/tumorigenicity (SCC context), replication-competent retrovirus; E&L of device components
“Integration site analysis in RDEB keratinocytes transduced with LZRSE-Col7A1 showed a low level of integration distributed throughout the host genome with no predilection to specific integration sites, including in genes associated with malignant transformation in humans.”