Jodi Y. So, MD

The treatment of recessive dystrophic epidermolysis bullosa (RDEB) with gene-corrected autologous keratinocyte grafts (EB-101) was found to be both safe and efficacious long-term, recent findings suggest.

RDEB is known for being a rare blistering genodermatosis known to cause severe wounds, the cause of which is COL7A1 gene mutations. Dermal-epidermal adhesion necessarily requires COL7A1.

This research was conducted to assess the use of EB-101 to treat the severe wounds and other effects of RDEB in patients.

The study was led by Jodi Y. So, MD, from Stanford University School of Medicine’s Department of Dermatology.

“Disease manifestations include severe and debilitating wounds, aggressive squamous cell carcinomas, and premature death; however, there are currently no approved therapies,” So and colleagues wrote. “This Phase 1/2a, open-label study evaluated the long-term efficacy and safety of gene-corrected autologous keratinocyte grafts (EB-101) for chronic RDEB wounds.”

Research and Methods

The research team conducted an open-label, phase 1 and 2a, non-randomized, single center, clinical trial on 7 participants.

It worked to treat chronic RDEB wounds through the use of keratinocyte sheets which expressed full-length C7.

The investigators collected keratinocytes from participants suffering from severe RDEB, and they were transduced with a retrovirus containing the full-length COL7A1 gene, and then grown into sheets.

If the 7 adults with severe RDEB wounds assessed in the study thad chronic wounds that had existed for ≥ 12 weeks, the researchers transplanted the gene-corrected keratinocyte sheets.

The patients with severe RDEB were each grafted with 6 sheets onto their wounds and the investigators followed them for a mean time of 5.9 years.

Study Findings

The data yielded from the study indicated long-term efficacy of EB-101, with the investigators noting that 21 out of 30 sites (70%) that were treated showed ≥ 50% wound healing compared to baseline by year 5.

The investigators also noted that compared to sites with < 50% wound healing, none of the 67% of wound sites with ≥ 50% wound healing were reported to be painful after 5 years (P < 0.001).

Additionally, the researchers noted over a mean of 5.9 years of follow-up, there were no adverse events reported.

Over the course of long-term follow-up meetings, they also noted that there was no persistent systemic autoimmunity against type VII collagen or replication-competent retrovirus infections, and none of the patients developed treatment-related cancers.

“In conclusion, autologous gene-corrected keratinocyte grafts may be a safe, durable treatment for chronic RDEB wounds, and the results of this Phase 1/2a trial demonstrate early evidence of sustained, long-term clinical benefit for patients with RDEB,” they wrote. “These results provide support that ex vivo cell therapy strategies may be viable approaches for RDEB and other monogenic genodermatoses.”

The study, “Long-term safety and efficacy of gene-corrected autologous keratinocyte grafts for recessive dystrophic epidermolysis bullosa,” was published online in the Orphanet Journal of Rare Diseases.