FDA Approves First Cell-Based Gene Therapy for Recessive Dystrophic Epidermolysis Bullosa

I am pleased to share that the FDA has approved prademagene zamikeracel (pz-cel), also known as Zevaskyn, the first autologous, cell-based gene therapy for recessive dystrophic epidermolysis bullosa (RDEB). This landmark approval represents a significant breakthrough for patients suffering from this devastating skin disorder. 

RDEB is a rare genetic condition in which patients lack functional Type VII collagen due to mutations in the COL7A1 gene. That results in extremely fragile skin that blisters easily, leading to painful chronic wounds, increased infection risk, and elevated skin cancer risk. Until recently, treatment options have been limited to wound care and pain management rather than addressing the underlying genetic cause. In 2023, however, FDA approved the gene therapy Vyjuvek, a topical gel that is applied weekly to the skin and contains a modified HSV-1 vector expressing COL7A1. Adding Zevaskyn to the RDEB treatment arsenal is another huge step forward. 

Zevaskyn is based on autologous keratinocytes (skin cells) that are genetically engineered to express functional COL7A1. The modified cells are expanded into keratin sheets and grafted directly onto wound areas. This one-time surgical application allows the corrected cells to produce the crucial Type VII collagen that forms anchoring fibrils between the epidermis and dermis. Importantly, the keratin sheet structure can be used to treat large chronic wounds. 

The approval follows an FDA review of clinical data from Abeona Therapeutics, including the pivotal Phase 3 VIITAL™ study and a Phase 1/2a study with up to eight years of follow-up. These studies demonstrated that Zevaskyn provided statistically significant improvements in wound healing and pain reduction in large chronic RDEB wounds. The therapy was well-tolerated with no serious treatment-related adverse events observed. Clinical data showed continuous Type VII collagen expression more than two years after treatment. In 2023, Zevaskyn received a Complete Response Letter (CRL) from FDA which was focused on CMC data; that prior rejection did not cite clinical or safety concerns. That the therapy was subsequently able to be re-submitted and approved reflects ongoing positive interactions between cell and gene therapy researchers and regulatory agencies that continue to advance the cell and gene therapy field. 

I want to extend my deepest gratitude to the RDEB patient community for their participation in clinical trials and the many researchers and funding agencies who dedicated years to understanding RDEB and developing this innovative therapy. This approval not only brings hope to those living with RDEB but also represents significant progress in general for gene-corrected cell therapies for rare genetic disorders. 

Paula Cannon, PhD, is the president of ASGCT (2024-25) and a Distinguished Professor of Molecular Microbiology & Immunology at USC's Keck School of Medicine. 

Related Articles