New approach to Tx of patients with recessive dystrophic epidermolysis bullosa

Dr. Jean Tang. Photo courtesy Stanford Medicine News

A phase 3 trial has demonstrated that a novel autologous gene-corrected cell therapy—prademagene zamikeracel—is effective in healing large, chronic wounds related to recessive dystrophic epidermolysis bullosa (RDEB). The study results were published in The Lancet.

The VIITAL study, conducted at Stanford University and the University of Massachusetts, enrolled 11 patients aged six years and older with confirmed RDEB, a rare condition characterized by blistering, non-healing wounds, and severe morbidity. Employing a rigorous intrapatient-controlled, randomized design, researchers compared prademagene zamikeracel—a surgically applied, retrovirally COL7A1-corrected autologous keratinocyte sheet—to standard of care within matched wound pairs, focusing exclusively on wounds larger than 20 cm².

At week 24, the data showed 81% of prademagene zamikeracel-treated wounds achieved at least 50% healing from baseline, compared to only 16% of wounds treated with standard care (mean difference 67%; p<0.0001). Complete wound healing at week 24 was documented in 16% of treated wounds versus none in controls. Pain reduction, measured with the Wong-Baker Faces scale, was similarly robust: the mean decrease in pain was –3.07 in the treatment arm, versus –0.90 in controls (mean difference –2.23; p=0.0002)—an improvement that surpassed U.S. FDA benchmarks for clinical relevance.

Adverse events were frequent but manageable, with no deaths or discontinuations. The majority of adverse events were mild to moderate, and only four patients experienced events deemed related to the gene-corrected graft, such as procedural pain or pruritus; all resolved without sequelae. No cases of systemic immunologic response, replication-competent retrovirus, or squamous cell carcinoma were linked to treated sites.

Unlike recently U.S. FDA-approved topical agents beremagene geperpavec and birch triterpenes, which require repeated application and are indicated for smaller wounds, prademagene zamikeracel is delivered as a single, surgically implanted sheet. This open-label trial—though limited by its small sample size and lack of blinding—could signal a paradigm shift for patients with historically untreatable, large, chronic RDEB wounds. The skin grafts were granted approval as an EB therapy on April 29 by the FDA.

“With our novel gene therapy technique, we successfully treated the hardest-to-heal wounds, which were usually also the most painful ones for these patients,” said the study’s lead author, Jean Tang, MD, PhD, in a press release. “It’s a dream come true for all the scientists, physicians, nurses, and patients who were involved in the long and difficult research process.” She is a professor of dermatology at Stanford who treats children with EB at Lucile Packard Children’s Hospital Stanford.

Patients with severe dystrophic epidermolysis bullosa have a defect in the gene for collagen VII, a protein that normally holds the skin together.

“Collagen VII is like a staple that attaches the top layer to the bottom layer of your skin,” Dr. Tang said. Without this molecular “staple,” the layers of patients’ skin separate in response to slight friction, causing wounds that can persist for years as well as extreme pain and itching.

Developed by Stanford University, prademagene zamikeracel was licensed from Stanford by Abeona Therapeutics Inc., which will manufacture the grafts.