D-Fi Gene Therapy for Dystrophic Epidermolysis Bullosa (DEB)

D-Fi Gene Therapy for Dystrophic Epidermolysis Bullosa (DEB)


At a Glance

  • A progressive, devastatingly painful and debilitating, genetic blistering disorder that is diagnosed at infancy and often leads to death
  • Current treatments – including bandaging and antibiotics – only address symptoms
  • Our investigational gene therapy (D-Fi) offers the potential to address the underlying cause of DEB by providing functional type VII collagen (COL7) locally to affected areas

About DEB

Dystrophic epidermolysis bullosa (DEB) is one of the four major types of epidermolysis bullosa (EB), a genetic connective tissue disorder that causes the skin to be extremely fragile. DEB results from mutations in the type VII collagen gene, or COL7A1, which encodes COL7. COL7—a protein—is the main component of anchoring fibrils, which anchor the basement membrane zone of the epidermis to the dermis, providing structural integrity to the skin at the dermal-epidermal junction. When functional COL7 is deficient, the anchoring fibrils cannot form properly.  Without these fibrils, skin layers separate causing blisters and wounds to form in response to any kind of friction or trauma, like rubbing or scratching.  

Recessive dystrophic epidermolysis bullosa (RDEB)—a severe form of DEB1—is a progressive, devastatingly painful and debilitating disorder. RDEB is an autosomal recessive disorder, meaning that a child has inherited copies of the defective gene from both parents3. Patients with RDEB typically show signs and symptoms shortly after birth and are diagnosed as newborns due to the severity of the disease. RDEB patients have the highest rate of morbidity and mortality of all genetic blistering disorders

Dominant dystrophic epidermolysis bullosa (DDEB) patients typically have higher levels of COL7A1 expression, resulting in milder signs and symptoms, with blistering often limited to the hands, feet, knees and elbows with mild scarring. Nevertheless, untreated symptoms may lead to serious complications, which could be fatal.

Presently, there are no U.S. Food and Drug Administration approved treatments for RDEB or DDEB, and treatment is generally limited to supportive care.

About D-Fi

D-Fi, also known as FCX-007, (dabocemagene autoficel), is being developed as an ex vivo, autologous cell-based gene therapy to address the deficiency of functional COL7 in patients with dystrophic epidermolysis bullosa (DEB).

D-Fi has been clinically studied in a Phase 1/2 clinical study (NCT02810951), which assessed 6 patients with RDEB. In this study, 80% (8/10) of treated chronic wounds demonstrated complete wound healing 12 weeks after the first injection of D-Fi, while none of the untreated wounds were healed.  D-Fi was well tolerated post-administration with few reports of temporary redness or discoloration at the injection site.

D-Fi is currently in Phase 3 clinical development for the localized treatment of chronic wounds in individuals with RDEB. The clinical study plan includes a multi-center, within-patient randomized, controlled, open-label study of D-Fi and builds on data reported from the Phase 1/2 clinical trial. For information about the Phase 3 Study, visit DeFi-RDEB.com.

The U. S. Food and Drug Administration has granted Orphan Drug designation to D-Fi for the treatment of Dystrophic Epidermolysis Bullosa, which includes RDEB. In addition, D-Fi has been granted Rare Pediatric Disease designation, Fast Track designation and Regenerative Medicine Advanced Therapy (RMAT) designation by the FDA for treatment of RDEB.

How Does D-Fi Gene Therapy Work?

Dermal fibroblasts are collected from the patient, cultured and genetically modified to provide functional COL7 and then injected locally into the affected areas. 

Learn more

Explore Advocacy & Educational Resources

  1. The Dystrophic Epidermolysis Bullosa Research Association of America. EB in Depth. https://www.debra.org/about-eb/eb-depth. Accessed July 2020
  2. Stanford Medicine, Epidermolysis Bullosa Clinic Frequently Asked Questions

Castle Creek Biosciences’ product candidates are investigational. None of our investigational gene therapies have received marketing approval by the U.S. Food and Drug Administration nor any other regulatory agency