Fibrocell Science of Exton, Pa., recently started a preclinical dose-ranging study for FCX-013, an investigational drug to treat linear scleroderma. The company expects to initiate a safety study and apply for Investigational New Drug (IND) status to the U.S. Food and Drug Administration (FDA) in late 2017. The design of both studies was based on feedback from the FDA.
Fibroblasts are the most common type of cells in the skin and connective tissue. These cells provide support and structure to tissues by producing several different proteins including collagen. Linear scleroderma, a form of localized scleroderma, is a chronic, autoimmune disorder characterized by overproduction of collagen type II and III proteins. Affected skin areas become too thick, and the condition can extend to underlying tissue and muscle. This hinders growth and development in children, and causes debilitating, painful symptoms.
Therapy with FCX-013 includes collecting skin fibroblasts from the patient, culturing them and then genetically modifying them to express a protein that controls collagen accumulation. The new fibroblasts are then injected at the site of the localized disease, where the protein breaks down excess collagen I and III proteins.
This therapy, designed in collaboration with Intrexon, uses the company’s proprietary RheoSwitch Therapeutic System, which lets researchers control future expression of the protein once fibrosis improves.
“We are pleased with the significant progress of our distinctive gene therapy candidates that have the potential to be transformative for patients suffering from rare and devastating genetic diseases of the skin and connective tissue,” Fibrocell CEO John Maslowski said in a press release. “We initiated a pre-clinical dose-ranging study for FCX-013, our gene therapy candidate for the treatment of linear scleroderma, and expect to follow with a toxicology/biodistribution study in the fourth quarter of 2017.”
The FDA granted Fibrocell orphan drug designation in 2016 to advance the development and testing of FCX-013 as a potential treatment for localized scleroderma. FCX-013 has been shown to reduce skin thickness of fibrotic tissue in a scleroderma rodent model.
Localized scleroderma comprises several forms and subtypes of the disease. About 200,000 Americans have the disease, including 40,000 with linear scleroderma over a major joint. Current treatments for linear scleroderma include systemic or topical corticosteroids, UVA light therapy and physical therapy, but these therapies only target disease symptoms.
FCX-013 is the first gene therapy under development to tackle the underlying cause of linear scleroderma and control collagen accumulation at the site of the localized disease.