Vyjuvek
beremagene geperpavec
Species
Mouse
Longest study
9 wk (derived)
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 (BALB/c) for GLP tox; single species
“the use of a single species (mice) for the toxicity studies is considered acceptable and in line with the”
Why that species
No justification given beyond historical use of mice; mouse skin dissimilar to human; EB mouse and human RDEB xenograft used for pharmacology
“A justification for the choice of mice is not specified, other than the suggestion that this species is historically used in toxicity studies.”
Surrogate molecule
No surrogate; clinical vector (KB103) tested in mice; human COL7 transgene
“In vivo Good Laboratory Practice (GLP) toxicology studies evaluated 1) single intravenous (IV) administration of VYJUVEK in BALB/c mice”
Study lengthopen answer page →
Longest pivotal study
9 (derived from the dosing and observation schedule)
“The remaining animals were sacrificed on Day 30 or allowed to recover for an additional 30 days following completion”
Pivotal GLP studies
GLP BALB/c mouse studies: single IV; 5 weekly intradermal doses with 30-day recovery; single topical to wounded skin
“five repeat weekly ID administrations of VYJUVEK in BALB/c mice at 6.9 x 106 or 3.45 x 107 pfu/mouse/administration”
Route in tox
Intradermal, topical (wounded skin) and intravenous (mice)
“single topical application of VYJUVEK mixed with 3% HPMC to wounded skin of BALB/c mice at 3.48 x 107 pfu/application.”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (HSV-1 does not integrate; negligible insertional mutagenesis)
“No traditional genotoxicity studies were performed.”
Carcinogenicity
Not conducted; weight-of-evidence literature risk assessment
“No carcinogenicity studies were performed, and the applicant provided a weight of evidence risk assessment”
Reproductive & developmental
Not conducted (acceptable given product characteristics and safety profile)
“Animal reproductive and developmental toxicity (DART) studies were not conducted with VYJUVEK.”
Safety pharmacology
Not conducted (locally administered, limited distribution)
“No safety pharmacology studies with KB-103 were performed.”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
NOAEL 6.9e6 pfu (low dose) in mouse intradermal study; dose-site scabbing, inflammatory lymphocyte hyperplasia; no adverse findings per FDA
“The low dose of 6.9 x 106 pfu was considered as the NOAEL.”
Risksopen answer page →
Immune & cytokine safety
Minimal to slight lymphoid hyperplasia in spleen and lymph nodes consistent with inflammatory response to vector
“microscopic findings of minimal to slight lymphocyte follicular hyperplasia in the spleen and minimal to slight lymphocyte hyperplasia in the axillary and/or inguinal lymph nodes were consistent with an inflammatory response to KB103”
Biodistribution & persistence
Vector mainly at application/injection site, declining to baseline by 30 days after last dose; not detected in other tissues after topical dosing
“resulted in vector detection primarily at the injection site, which declined to baseline by 30 days after the last dose.”
Modality-specific risk
Replication-defective non-integrating HSV-1 vector: local inflammatory/immune reaction, limited systemic distribution; shedding assessed clinically
“No non-clinical studies investigating excretion of KB103 were conducted, and vector shedding was studied in the clinical setting.”