Recent data presented at the Society for Investigative Dermatology (SID) conference demonstrated that EB-101, a gene therapy provided significant wound healing in patients with Recessive Dystrophic Epidermolysis Bullosa (RDEB), a severe form of epidermolysis bullosa (EB).
RDEB is a subtype of an inherited genetic skin disorder characterized by chronic skin blistering, open and painful wounds, joint contractures, esophageal strictures, pseudosyndactyly, corneal abrasions and a shortened life span. Patients with RDEB lack functional type VII collagen owing to mutations in the gene COL7A1 that encodes for C7 and is the main component of anchoring fibrils, which stabilize the dermal-epidermal basement membrane
EB-101 is an autologous, ex-vivo gene therapy in which COL7A1 is transduced into autologous keratinocytes for the treatment of Recessive Dystrophic Epidermolysis Bullosa (RDEB).
The therapy provided healing (defined as greater than 50% healed) in 100% of Treated Wounds (36/36) at 3 Months; 89% (32/36) at 6 months, 83% (20/24) at 12 months, 88% (21/24) at 24 Months and 100% (6/6) at 36 months Post-Administration. The findings were presented by Abeona Therapeutics’ a leading clinical-stage biopharmaceutical company focused on developing novel gene therapies for life-threatening rare diseases, and the scientific and clinical collaborators at Stanford University School of Medicine, a center of excellence for the treatment of patients with epidermolysis bullosa.
The company also unveiled updated clinical data from the ongoing Phase 1/2 clinical trial for the EB-101 gene therapy program for patients with, along with supportive natural history data for 128 patients with the fatal skin disease.
“Last week at the SID conference, our EB-101 team of clinical investigators and scientific collaborators presented data from the ongoing Phase 1/2 gene therapy clinical trial and a supportive natural history study of patients with RDEB that highlight the unprecedented wound healing and durable collagen C7 expression of four patients through two years’ post-treatment, including one patient that has continued to see EB-101 treated wounds remain healed three years post-treatment. The relevance of these benefits is highlighted when compared to non-treated control wounds evaluated from the 128-patient natural history study, which showed that RBEB patients suffer chronic and recurrent wounds that do not heal on their own and persist for several years,” said Timothy J. Miller, Ph.D., President and CEO of Abeona Therapeutics.
In the Phase 1/2 trial, EB-101 was administered to non-healing chronic wounds [mean length of time wounds were unhealed (unclosed) was 8.5 years prior to the gene therapy administration] on each subject and assessed for wound healing at predefined time points over years. The primary endpoint of the clinical trial is to assess safety and evaluate wound closure after EB-101 administration compared to control untreated wounds. Secondary endpoints include expression of full-length collagen C7 and restoration of anchoring fibrils at three and six months’ post-administration.
As reflected at the conference by Stanford collaborators, wounds were evaluated at three, six, 12, 24 and 36 months for appearance, durability, and resistance to blistering**:
Wound healing >50%: defined as >50% closure after EB-101 administration was observed in:
– 100% (36/36 treated wounds, n=6 subjects) at 3 months;
– 89% (32/36 treated wounds, n=6 subjects) at 6 months;
– 83% (20/24 treated wounds, n=4 subjects) at 12 months,
– 88% (21/24 treated wounds, n=4 subjects) at 24 months,
– 100% (6/6 treated wounds, n=1 subject) at 36 months post-administration.
Wound healing >75%: defined as >75% closure after EB-101 administration was observed in:
– 83% (30/36 treated wounds, n=6 subjects) at 3 months;
– 61% (22/36 treated wounds, n=6 subjects) at 6 months;
– 50% (12/24 treated wounds, n=4 subjects) at 12 months;
– 71% (17/24 treated wounds, n=4 subjects) at 24 months;
– 83% (5/6 treated wounds, n=1 subject) at 36 months post-administration.
Collagen VII (C7) expression observed: C7 and morphologically normal NC2 reactive anchoring fibrils – the “zipper” that holds skin onto the underlying tissue and the primary deficit in RDEB patients – have been observed in EB-101 treatments up to two years post administration.
Natural History Study
Data from a supportive natural history study of 1,436 wounds of 128 patients with RDEB, established by Stanford and EBCare Registry, were also presented at the conference. The natural history study characterized both chronic non-healing wounds, defined as an area that does not heal ≥12 weeks, and recurrent wounds, defined as an area that partially heals but then easily re-blisters. Results presented were characterized as 1041 recurrent wounds and 395 chronic open wounds.
Notably, in the natural history study, 13 RDEB patients with a total of 15 chronic wounds were treated with an allograft product, including Apligraf® and Dermagraft®***. Of these wounds treated with allografts, only 7% (1/15 treated wounds) remained healed after 12 weeks, and 0% (0/15 treated wounds) remained healed after 24 weeks. This is a meaningful finding of the natural history study, as there are no approved therapies for RDEB patients that demonstrate significant wound closure after two months post-application.
Investigators at Stanford University are enrolling patients for the ongoing Phase 2 portion of the Phase 1/2 clinical trial (NCT01263379). The EB-101 program has been granted orphan drug designation from the European Medicines Agency (EMA).
Image credit: Samantha Okazaki / Today