Prademagene zamikeracel

In patients with recessive dystrophic epidermolysis bullosa (RDEB), both copies of the COL7A1 gene are mutated, resulting in the absence or low levels of biologically active C7 protein which form anchoring fibrils (AFs). The lack of AFs disrupts the connection between the epidermis and the dermis and causes skin fragility and other signs and symptoms of RDEB. Prademagene zamikeracel consists of a patient's own cells that have been gene-modified through RVV transduction to express the COL7A1 gene to produce the C7 protein. These cells are formed into cellular sheets for topical application onto wounds.

In a single-arm clinical study (n=7), C7 was assessed by both immunofluorescence and the presence of AFs at Months 3, 6, and 12. The NC2 domain of C7 was assessed using the LH24 antibody, and the presence of AFs was assessed by immunoelectron microscopy. The NC2 domain of C7 and AFs were detected in 6 patients at 3 months and in 5 patients at 6 months. One year after treatment with prademagene zamikeracel, 3 patients were positive for NC2 or AFs. At Year 2, 2 out of 3 patients with biopsies were positive for NC2 or AFs (1 patient was positive for both AFs and NC2; the second patient was positive only for NC2, as an additional biopsy for AF assessment was not obtained).

No clinical studies have been conducted to evaluate the pharmacokinetics of prademagene zamikeracel.