Gene Therapy for Moderate to Severe Localized Scleroderma Granted Fast Track Designation

The US Food and Drug Administration (FDA) has granted a fast track designation to Fibrocell Science, Inc.’s candidate, FCX-013, for the treatment of patients with moderate to severe localized scleroderma, a rare genetic skin disorder for which there are no approved therapies available.

“Fast Track designation represents an important milestone in advancing clinical development of FCX-013,” John Maslowski, Fibrocell’s president and chief executive officer, said in a recent statement. “We are pleased the FDA has awarded this designation to FCX-013 which, we believe, has the potential to be the first gene therapy to treat excessive collagen accumulation in the skin and soft tissue at the site of localized scleroderma lesions and to bring relief from the severe pain and functional disability associated with the disorder.”

The gene therapy, FCX-013, is an autologous fibroblast that has been genetically modified and encoded for matrix metalloproteinase 1, a protein that breaks down collagen. By incorporating Precigen’s RheoSwitch Therapeutic System—a biologic switch that is activated by Veledimex, an oral compound—FCX-013 is able to control protein expression at the site of the localized legions.

“FCX-013 is designed to be injected under the skin at the location of the fibrotic lesions where the genetically-modified fibroblast cells will produce MMP-1 to break down excess collagen accumulation,” according to Fibrocell.

With this therapy, patients will take Veledimex in order to facilitate protein expression and then, once the fibrosis is resolved, they will stop taking the compound; by doing this, they will control further MMP-1 production.

In August 2018, Fibrocell initiated the first investigator site for clinical enrollment for an open-label, single-arm phase 1/2 clinical trial designed to evaluate the safety of FCX-013 in patients with scleroderma. For the trial, investigators will conduct fibrosis assessments, including histology, skin scores, and ultrasound. Post-administration of FCX-013, they will measure targeted sclerotic lesions and control sites at different time points for the duration of 16 weeks.

A total of 10 patients who have a subtype of localized scleroderma are targeted for enrollment, with about 5 patients per phase. For the phase 1 portion of the trial, adult patients will be enrolled; they will stagger the dosing of the first 3 patients before dosing the rest of the participants. Pediatric patients will be included in the phase 2 portion of the trial, following submission and approval of safety and activity data gleaned from the adult patients included in phase 1 and the Data Safety Monitoring Board for the trial.

The FDA granted an orphan drug designation to FCX-013 for the treatment of localized scleroderma as well as a rare pediatric disease designation for the treatment of moderate to severe localized scleroderma.