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Long-term safety and efficacy of gene-corrected autologous keratinocyte grafts for recessive dystrophic epidermolysis bullosa.


ABSTRACT:

Background

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare, devastating blistering genodermatosis caused by mutations in the COL7A1 gene, which encodes for type VII collagen and is necessary for dermal-epidermal adhesion and integrity. Disease manifestations include severe and debilitating wounds, aggressive squamous cell carcinomas, and premature death; however, there are currently no approved therapies. 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.

Methods

Autologous keratinocytes were harvested from participants with severe RDEB, transduced with a retrovirus containing the full-length COL7A1 gene, and grown into 5 × 7 cm (35 cm2) sheets. Gene-corrected keratinocyte sheets were then transplanted onto chronic RDEB wounds present for ≥ 12 weeks.

Results

Seven adult participants with severe RDEB were grafted with six sheets each (42 total sheets) onto wounds and followed for a mean of 5.9 years (range 4-8 years). Long-term improvements in wound healing and symptoms were observed. At year five, 70% (21/30) of treated sites demonstrated ≥ 50% wound healing compared to baseline by investigator global assessment. No sites with ≥ 50% wound healing were painful or pruritic, compared to 67% (6/9) of sites with < 50% wound healing (p < 0.001) at year five. Grafts were well-tolerated throughout long-term follow-up. No serious adverse events related to treatment were reported over a mean of 5.9 years of follow-up. No persistent systemic autoimmunity against type VII collagen or replication-competent retrovirus infections were identified, and no participants developed squamous cell carcinomas related to treatment during long-term follow-up.

Conclusions

Treatment with EB-101 appears safe and efficacious, and produces long-term improvements in wound healing, pain, and itch for RDEB patients. Results from the Phase 3 randomized controlled trial are forthcoming.

Trial registration

ClinicalTrials.gov, NCT01263379. Registered December 15, 2010. https://clinicaltrials.gov/ct2/show/NCT01263379.

SUBMITTER: So JY 

PROVIDER: S-EPMC9574807 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Long-term safety and efficacy of gene-corrected autologous keratinocyte grafts for recessive dystrophic epidermolysis bullosa.

So Jodi Y JY   Nazaroff Jaron J   Iwummadu Chinonso V CV   Harris Nicki N   Gorell Emily S ES   Fulchand Shivali S   Bailey Irene I   McCarthy Daniel D   Siprashvili Zurab Z   Marinkovich M Peter MP   Tang Jean Y JY   Chiou Albert S AS  

Orphanet journal of rare diseases 20221017 1


<h4>Background</h4>Recessive dystrophic epidermolysis bullosa (RDEB) is a rare, devastating blistering genodermatosis caused by mutations in the COL7A1 gene, which encodes for type VII collagen and is necessary for dermal-epidermal adhesion and integrity. Disease manifestations include severe and debilitating wounds, aggressive squamous cell carcinomas, and premature death; however, there are currently no approved therapies. This Phase 1/2a, open-label study evaluated the long-term efficacy and  ...[more]

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