Phase 1/2a Clinical Trial of Gene-Corrected Autologous Cell Therapy for Recessive Dystrophic Epidermolysis Bullosa
Shaundra Eichstadt, MD, Stanford University Department of Dermatology, Redwood City, California; Tufts University Medical Center, Boston, Massachusetts
Disclosures: None.
Recessive dystrophic epidermolysis bullosa (RDEB) patients have mutations in the COL7A1 gene, thus lacking functional type VII collagen (C7) protein; they have marked skin fragility and blistering. This single-center phase 1/2a open-label study evaluated the long-term efficacy, safety, and patient-reported outcomes in RDEB patients treated with gene-corrected autologous cell therapy (ClinicalTrials.gov identifier NCT01263379). Autologous keratinocytes were isolated from participant skin biopsies. Epidermal sheets were prepared from cells transduced with a retrovirus carrying the full-length human COL7A1 gene. These gene-corrected autologous epidermal sheets measured 5×7 cm (35 cm2) and were transplanted onto 6 wound sites in each of 7 adult participants (N=42 sites) between 2013 and 2017. Participants were followed for 2 to 5 years. No participants experienced any serious related adverse events. Wound healing of 50% or more by Investigator Global Assessment was present in 95% (36/38) of treated wounds versus 0% (0/6) of untreated control wounds at 6 months (P<.0001). At year 1, 68% (26/38) of treated wounds had healing of 50% or more compared with 17% (1/6) of control wounds (P=.025). At year 2, 71% (27/38) of treated wounds had healing of 50% or more compared with 17% (1/6) of control wounds (P=.019). C7 expression persisted up to 2 years posttreatment in 2 participants. Treated wounds with 50% or more wound healing demonstrated improvement in patient-reported pain, itch, and wound durability. This study provides additional data to support the clinically meaningful benefit of treating chronic RDEB wounds with ex vivo, C7 gene-corrected autologous cell therapy. This approach was safe and promoted wound healing that was associated with improved patient-reported outcomes.
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