Zevaskyn (prademagene zamikeracel): what was done before first-in-human, and what came after?

Precedia/Gene therapy/Zevaskyn/Tox package

Zevaskyn: what was done before first-in-human, and what came after?

prademagene zamikeracel · COL7A1 (RV-modified keratinocyte sheets)

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 Zevaskyn 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 gene 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 gross or histopathological findings in any tissue, including explanted products; no NOAEL stated (FDA summary basis for approval, p. 13)

Full method, every step sourced →

Longest repeat-dose systemic studies

Longest repeat-dose study and recovery

No repeat-dose study (single implantation); mouse toxicology/biodistribution study with 4- or 8-week sacrifice

“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.”

✓ VerifiedFDA summary basis for approval, p. 12Source ↗

Pivotal GLP studies

One combined toxicology/biodistribution study in mice, implantation into excisional wounds, 4- and 8-week sacrifices

✓ VerifiedFDA summary basis for approval, p. 12Source ↗

DART package

Species: DART

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.”