Clinical Trials

Date: 2017-05-02

Type of information: Presentation of results at a congress

phase: 1-2

Announcement: presentation of results at the Society for Investigative Dermatology (SID) conference

Company: Abeona Therapeutics (USA - NY)

Product: EB-101 (gene corrected skin grafts)

Action mechanism: gene therapy. 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.

Disease: epidermolysis bullosa

Therapeutic area: Rare diseases - Genetic diseases - Dermatological diseases

Country: USA

Trial details: This trial will create a skin graft, which the investigators call "LEAES," using the patient's own skin cells that have been genetically engineered in the lab to express a missing protein called type VII collagen. The corrected cells will be transplanted back to the patient. (NCT01263379).

Latest news:

• • On May 2, 2017, Abeona Therapeutics announced updated clinical data from the ongoing Phase 1/2 clinical trial for the EB-101 gene therapy program for patients with Recessive Dystrophic Epidermolysis Bullosa (RDEB), along with supportive natural history data for 128 patients with the fatal skin disease. These data were presented at the recently held Society for Investigative Dermatology (SID) conference by Abeona’s scientific and clinical collaborators at Stanford University School of Medicine.
• In the Phase 1/2 trial, EB-101 was administered to non-healing chronic wounds [mean length of time wounds were unhealed 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.
• 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.
• • On November 2, 2016, Abeona Therapeutics announced that positive clinical trial results from the EB-101 Phase I gene therapy clinical trial were published as "Safety and wound outcomes following genetically corrected autologous epidermal grafts in patients with recessive dystrophic epidermolysis bullosa" in the Journal of the American Medical Association (JAMA). Typically, wounds in patients with recessive dystrophic epidermolysis bullosa can remain unhealed for months to years due to the inability of the skin to stay attached to the underlying dermis and can cover a large percentage of the body. Results from the clinical study demonstrated that treatment with EB-101 restored Type VII collagen expression at the dermal-epidermal junction at the graft sites in 90% of the biopsy samples at 3 months post-treatment, in 66% at 6 months post-treatment, and in 42% samples at 12 months post-treatment. Importantly, correct type VII collagen localization was observed at anchoring fibrils. Wounds that demonstrated type VII collagen at graft sites displayed 87% healing at 3 months, 67% at 6 months, 50% at 12 months compared with baseline wound sites. Investigators at Stanford University are enrolling adolescent and adult patients for the Phase 2 EB-101 trial to determine the safety and efficacy of COL7A1 gene-corrected grafts on wound healing.
• • On September 29, 2016, Abeona Therapeutics announced that phase 1 clinical trial in five patients demonstrated EB-101 (gene corrected skin grafts) was well tolerated and demonstrated promising clinical efficacy in patients for the treatment of recessive dystrophic epidermolysis bullosa. Significant improvements in wound healing and gene expression observed up to 12 months post-treatment. Now the first patient was enrolled in the Phase 2 portion of the clinical trial.
• • On September 8, 2016, Abeona Therapeutics announced that the fifth patient was enrolled in the Phase 1/2 clinical trial for EB-101 (gene-corrected skin grafts). EB-101 is the Company's lead gene therapy program for patients suffering with recessive dystrophic epidermolysis bullosa, a severe form of epidermolysis bullosa (EB). Also known as "Butterfly skin" syndrome, RDEB is a rare genetic skin disease that is caused by the absence of a gene (COL7A1) which encodes a protein known as type VII collagen (C7). Patients with RDEB develop large, severely painful blisters and chronic wounds from minor trauma to their skin and currently no FDA approved treatments for RDEB. The Phase 1/2 clinical trial with gene-corrected skin grafts has shown promising wound healing and safety in patients with RDEB. Investigators at Stanford are now expanding enrollment to adolescent patients for the Phase 1/2 trial to determine the safety and efficacy of COL7A1 gene-corrected grafts on wound healing efficacy. Clinical data on the initial four patients in the Phase 1/2 trial were recently presented at the opening Plenary Session of the Society for Investigative Dermatology.

Is general: Yes