The experimental cell therapy EB-101 was safe and led to successful wound healing in seven adults with recessive dystrophic epidermolysis bullosa (RDEB), followed-up for five years, the results of a Phase 1/2a clinical trial show.
The study detailing the results, “Phase 1/2a clinical trial of gene-corrected autologous cell therapy for recessive dystrophic epidermolysis bullosa,” was published in the journal JCI Insight.
RDEB is a rare form of epidermolysis bullosa characterized by easy skin blistering, recurrent wounds, and frequent wound infections. The disorder is caused by inherited mutations in the COL7A1 gene, which leads to a deficiency in type 7 collagen (COL7).
EB-101 is a gene-corrected cell therapy therapy developed by Abeona Therapeutics. It delivers a correct version of the COL7A1 gene through non-infectious viral carriers to the patient’s own skin cells (keratinocytes), collected from skin biopsies and cultured in a lab dish. These genetically engineered cells are then transplanted back to the patient, restoring normal COL7 production in the skin.
The Phase 1/2a trial (NCT01263379), conducted at Stanford University, is evaluating the long-term efficacy and safety of EB-101 for treating chronic wounds in adults with RDEB. The study includes seven adults, ages 18 to 45, with severe, generalized RDEB and an estimated wounded body surface area ranging from 4% to 30%.
Each patient received a skin cell transplant onto six chronic wounds, which had been present from three to 20 years prior to treatment.
Transplants were conducted from 2013 to 2017. All 42 treated sites were monitored for wound healing, infection, pain, itch, durability, and ease of blistering for up to five years.
The trial’s primary goals are to assess whether EB-101 is safe and able to heal wounds. It is estimated to be completed by December 2025.
In line with previously reported results, 95% of treated sites had 50% or greater healing at three and six months, compared with no healing observed in untreated wounds. The proportion of wound healing was 68% after the first year, 71% at two years, and 80% at three years.
This contrasted with 17% of healing in untreated wounds at one and two years after the transplant.
Researchers noted that large, older wounds may be more challenging to heal with this technique. At two years, only 56% of wounds that had been present for 16 years or longer achieved 50% or greater healing compared with 85% of chronic open wounds lasting for less than 15 years.
EB-101 repair activity was accompanied by a sustained production of COL7 in patients’ skin cells, up to two years after treatment.
At 12 months, three participants showed signs of COL7 restoration, as measured by the production of anchoring fibrils — filaments made of COL7 that are critical for linking the epidermis to the dermis, or the outer skin layers. Two years after treatment, two of these patients maintained fibrils production.
Pain and itching were eased due to EB-101. On treated sites with 50% or greater wound healing, participants completely stopped having pain at one and three years. At two years, they reported pain in 4% of their treated wounds.
Likewise, itching reduced from 61% of wounds prior to treatment to 19% of treated sites at one year, 7% at two years, and none at three years.
EB-101 was well-tolerated and did not pose any serious treatment-related side effects. The most common related adverse events were infection of the treated site (two patients), itch around the treated site (three patients), and pain around the treated site (one patient).
“This study provides additional data to support the clinically meaningful benefit of treating chronic RDEB wounds with [EB-101] cell therapy,” the researchers said.
The absence of harmful viral replication — a rare but possible side effect of virus-mediated gene correction — up to five years “is reassuring,” they added.
Due to concerns about EB-101’s stability during transport to clinical sites, the initiation of a Phase 3 trial was put on hold by the FDA in September. The company said it remains committed to advancing EB-101 and is working closely with the FDA to resolve the transport issues.