Cell-based, gene therapy skin grafts heal large epidermolysis bullosa wounds

Key takeaways:

• A cell-based, gene therapy skin graft healed large chronic wounds for patients with epidermolysis bullosa.
• The technology could be the catalyst for similar research in other genetic diseases.

Genetically engineered skin grafts exhibited a long-term ability to heal large, chronic wounds in patients with recessive dystrophic epidermolysis bullosa, according to study results published in The Lancet.

“Epidermolysis bullosa (EB) is a family of diseases, with dystrophic EB being one of the more severe variants,” Peter Marinkovich, MD, associate professor of dermatology at Stanford University School of Medicine and coprincipal investigator of the study, told Healio. “These patients are born with painful blisters all over their body and sometimes inside their mouth. When the blisters heal, they heal with scarring that can produce deformities.”

Prademagene zamikeracel (Zevaskyn, Abeona Therapeutics), a genetically engineered skin graft, was approved by the FDA April 29. It is the second therapy indicated for EB after beremagene geperpavec-svdt (Vyjuvek, Krystal Biotech), which was approved May 19, 2023, as Healio previously reported.

Beremagene geperpavec-svdt, a gene therapy gel, offered relief and healing for smaller wounds; however, patients with larger, more persistent wounds were still without effective treatment Marinkovich said.

“These patients have had nothing other than wound care and supportive care until recently,” Marinkovich said. “Now, with these gene therapies, we can reverse the blistering and actually correct the disease.”

Jean Y. Tang

Developed at Stanford, prademagene zamikeracel works by genetically modifying grafts of the patient’s own skin cells, adding a functional COL7A1 gene, which was previously mutated in patients with EB. As the first-ever gene therapy that uses patients’ own corrected skin cells, prademagene zamikeracel’s technology could be the catalyst for similar research in other genetic diseases, according to Jean Y. Tang, MD, PhD, professor of dermatology at Stanford University School of Medicine and a co-principal investigator of the study.

“This gene therapy skin approach shows the possibility of taking a skin biopsy from the patient, correcting the genetic problem and then putting the gene-corrected ‘stronger’ skin onto the patient to help fix their disease,” Tang told Healio. “This method could work for other genetic diseases.”

The phase 3 VIITAL study included 11 participants with recessive dystrophic EB, with 86 wounds. Researchers randomly assigned participants to either prademagene zamikeracel treatment (n = 43) or control (n = 43).

By week 24, results showed that 81% of the wounds treated with prademagene zamikeracel were at least 50% healed from baseline vs. 16% of the control wounds. At the same time point, 65% of the prademagene zamikeracel-treated wounds were also at least 75% healed compared with 7% of controls.

The improvement in pain from baseline to week 24 among participants treated with prademagene zamikeracel was nearly three times that of control participants (–3.07 vs. –0.9), according to the Wong-Baker Faces scale. All participants experienced at least one adverse event, the majority of which were mild or moderate in severity. No serious events were related to the skin graft.

Although this new technology fills huge gaps in EB care, more research is needed, particularly for pediatric patients, according to Tang and Marinkovich.

“We are all interested in seeing how [prademagene zamikeracel] affects patients’ wounds and lives in the real world,” Tang said. “The phase 3 trial only had two pediatric patients, and we are hopeful that there could be more wound healing response in younger patients. We are excited that there are new drugs to help EB patients’ skin, but the goal is to find a gene therapy that fixes all of their cells and helps heal EB patients’ eyes, throats and internal wounds.”

According to Marinkovich, treatment accessibility could pose a barrier to care.

“The hope is that it can be approved by insurance so that all patients in the United States have access to this therapy,” Marinkovich said. “Additionally, this procedure is not something that can be done in a local community hospital. There will be a handful of centers in the United States, maybe five or six, that will have experience working with EB patients. The expectation is that the patients will need to be transported to one of these centers.”

Prademagene zamikeracel offers patients the possibility of durable healing, Tang said.

“EB patients suffer tremendously … children are wrapped head to toe in bandages because their skin is so fragile like butterfly wings,” Tang told Healio. “I think most dermatologists would be glad that there is finally something for large EB wounds.”

For more information:

Jean Y. Tang, MD, PhD, and Peter Marinkovich, MD, can be reached at tangy@stanford.edu.