A Pivotal Phase 3 Study of FCX-007 (Genetically-Modified Autologous Human Dermal Fibroblasts) for Recessive Dystrophic Epidermolysis Bullosa

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7. PROJECT SUMMARY/ABSTRACT Recessive dystrophic epidermolysis bullosa (RDEB), is an autosomal recessive, inherited skin disease caused by mutations within the type VII collagen gene. The disease is characterized by painful blisters and wounds on skin and mucous membranes due to lack of adhesion of the epidermis to the inner dermal layers of the skin. The sequelae of wounds are often debilitating, disfiguring, and sometimes fatal. RDEB patients have a reduced life expectancy with early death resulting from infection, organ failure or squamous cell carcinoma (SCC). Current therapy for RDEB is limited to palliative wound care as there are currently no approved drugs for RDEB. Fibrocell Technologies, Inc. (FTI) is developing FCX-007, a suspension of live, ex-vivo, autologous human dermal fibroblast cells that have been genetically modified using a lentiviral vector (INXN-2004), which enables the expression of the human type VII (C7) protein. FTI has an open Investigational New Drug Application (IND 016582) for FCX-007. FTI proposes to continue its interventional, intra-patient randomized and controlled, open-label, Phase 3 study to evaluate the efficacy, durability, and safety of FCX-007. FTI has worked closely with the FDA in designing the Phase 3 clinical trial based on data gathered from the Phase 1/2 trial (FI-EB-001). Clinical efficacy will be determined by blinded investigator assessment of complete wound closure, durability of response, change in surface area of wound, and a patient reported outcome of pain. Clinical safety will be assessed by testing for presence of replication-competent lentivirus (RCL), type VII collagen autoantibody immune reactions, neoplasms (squamous cell carcinoma (SCC)), as well as physical examinations and adverse events (AEs). Efficacy and durability of FCX-007 will be assessed by the closure of wounds from Week 12 through Week 48, which FTI believes represents a clinically meaningful benefit to study subjects. FTI expects FCX-007 to be clinically safe given the FCX-007 Phase 1/2 clinical data (FI-EB-001), the preclinical safety data, and the autologous nature of the therapy. FCX-007 has been granted Orphan, Rare Pediatric Disease, and Regenerative Medicine Advanced Therapy (RMAT) designations by the FDA for the treatment of subjects with RDEB. The grant funding will be used to execute the Phase 3 clinical trial (FI-EB-002) which may lead to a potentially effective cell-based gene therapy for RDEB subjects. This grant proposal fulfills the goal of FDA's Office Orphan Product Development grant program to support the clinical development of products for use in rare diseases where no current therapy exists.