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Personalized biologics for rare skin disease
November 2017
by Ilene Schneider  |  Email the author


EXTON, Pa.—Fibrocell Science Inc., which uses proprietary transformational autologous fibroblast technology as the foundation for creating personalized biologics for diseases of the skin and connective tissue, has reported interim results in its Phase 1/2 clinical trial of FCX-007 for the treatment of recessive dystrophic epidermolysis bullosa (RDEB).
RDEB is a rare skin-blistering disorder that is an inherited genetic mutation from one’s parents. The congenital and progressive orphan skin disease is caused by the deficiency of the protein type VII collagen (COL7). The body is unable to make the protein for the anchoring fibril. Any friction causes blisters. There is pain, fracture, disease of the mouth and mucosa and high mortality from squamous cell carcinoma by age 30. Autologous fibroblasts use the patient’s own cells as a carrier of gene therapy, replacing COL7.
By genetically modifying autologous fibroblasts ex-vivo to produce COL7, culturing them and then treating wounds locally via injection, FCX-007 offers the potential to address the underlying cause of the disease by providing high levels of COL7 directly to the affected areas while avoiding systemic distribution. FCX-007 has been granted Orphan Drug, Rare Pediatric Disease and Fast Track designations by the U.S. Food and Drug Administration (FDA).
“FCX-007, Fibrocell's clinical-stage gene therapy product candidate for the treatment of RDEB, has shown encouraging safety and positive early trends in pharmacology and wound healing with only a single injection session of cells,” stated John Maslowski, president and CEO of Fibrocell. “These interim results are a positive step towards our ultimate goal of bringing relief to patients and families suffering from this debilitating disease. In the coming months, we look forward to performing additional dosing and enhancing COL7 expression, and working with the FDA to further advance the program.”
In the study three adult non-collagenous (NC)1+ patients were dosed with a single intradermal injection session of FCX-007 in the margins of and across targeted wounds, as well as in separate intact skin sites. Five wounds were treated on the three subjects, and FCX-007 appeared to be well tolerated through 12 weeks post-administration with no serious adverse events.
Wounds that were evaluated during a monitoring period before dosing appeared to be open for up to eight months. Compared to the baseline measurement collected before the single intradermal injection session of FCX-007, at four weeks post-administration 100 percent (5/5) of wounds were more than 75 percent healed. At 12 weeks post-administration, 80 percent (4/5) of wounds were more than 70 percent healed.
Various pharmacology signals for vector DNA, COL7 mRNA, or COL7 protein expression were detected throughout the data set in each patient for one or more assays up to 12 weeks post-administration (qPCR, electron microscopy or immunofluorescence). Anchoring fibrils have not been detected to date, whereas expressed COL7 mRNA and COL7 protein have been confirmed in multiple patient samples including one that detected linear expression of COL7 at the basement membrane zone.
With data from the first three patients meeting the primary trial objective of safety, Fibrocell plans to increase expression and dosing of FCX-007. Fibrocell’s gene therapy portfolio is being developed in collaboration with Intrexon Corp., a leader in synthetic biology. According to Maslowski, “Autologous fibroblasts were approved as cell therapy for aesthetics in 2011. We were approached by Intrexon to use the cells to reapply for FDA approval to use the genes for rare genetic disorders.”
Fibroblasts are the basis of Fibrocell’s personalized cell and gene therapy platform because they are the most common cell in skin and connective tissue and are responsible for synthesizing extracellular matrix proteins, including collagen, that provide structure and support.
Fibrocell’s autologous fibroblast technology uses a patented manufacturing process, which involves collecting small skin biopsies from patients, isolating cells and expanding them in culture, then transducing the fibroblast cells with an integrative lentiviral vector to express a targeted protein, followed by continued expansion of the gene-modified cells in culture. In this manner, each patient is treated with cells that were cultivated from his or her own dermal tissue.
Another product, FCX-013—which has Orphan Drug and Rare Pediatric Disease designations—is being developed for moderate to severe localized scleroderma, a disease that affects mobility and development of children and can cause neurological and ocular disorders. An IND filing is expected in the fourth quarter of 2017, and a GLP biodistribution/toxicology study is ongoing.
Fibrocell is also looking at treating arthritis and related conditions. The company anticipates delivering therapeutic protein locally to the joint, providing sustained efficacy while avoiding key side effects typically associated with systemic therapy.
“Gene therapy is now a reality,” Maslowski concluded. “We’ve developed a platform technology for skin and tissue diseases. We can show benefit and show follow-up.”
Code: E111717



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