ZEVASKYN  (Prademagene zamikeracel)

[Dystrophic epidermolysis bullosa (DEB) is caused by mutations in the collagen type VII alpha 1 chain (COL7A1) gene which results in reduced or absent levels of human type VII collagen (COL7) protein. The COL7 molecule arranges into bungles that form anchoring fibrils. The anchoring fibrils hold the epidermis and dermis together to maintain the integrity of the skin. Patients with autosomal dominant DEB have lower than normal functional anchoring fibrils and patients with recessive DEB have no functional anchoring fibrils which manifests as a more severe form the disease. Clinical manifestations of severe disease include fragility of the skin and mucosal surfaces which result in recurrent blisters, chronic wounds, and/or erosions of the skin and/or oral mucosa that result in severe scarring, deformities (e.g. fusion of skin, loss of nails, contractures, hair loss), and infection. Pruritis is common which makes healing difficult if there is trauma from scratching. Esophageal erosions and strictures are a common feature which lead to painful dysphagia and subsequent nutritional deficiencies, electrolyte abnormalities, and anemia. Genitourinary erosions may result in urinary retention and scarring of ocular mucosal membranes can result in vision loss. Patients with the recessive form of DEB are at higher risk of developing aggressive squamous cell carcinomas (SCC) at chronic wound sites and mortality from SCC has been estimated at 84% by 40 years of age. Supportive treatment of DEB includes wound care, control of pruritis and pain, preventing infection, nutritional support, and control of any additional presenting symptoms. Prademagene zamikeracel (Zevaskyn) is an autologous cell sheet-based gene therapy indicated for the treatment of wounds in adult and pediatric patients with recessive dystrophic epidermolysis bullosa (RDEB). Skin biopsies of a patient with RDEB are genetically modified through retroviral vector (RVV) transduction to express a the COL7A1 gene to produce the functional collagen VII (COL7) protein. The cells are formed into cellular sheets which is applied topically to the wound. The efficacy of prademagene zamikeracel was evaluated as compared to standard-of-care wound dressings in patients with RDEB in a multi-center, randomized, intrapatient-controlled trial. There were 86 RDEB wounds in 11 patients treated. Patients were required to have at least one pair of matched chronic large wounds (greater than or equal to 20 cm2 and open for at 6 months or more). Patients were age 6 to 50, including two pediatric patients age 6 and 16. The wounds had been open for a median of 5 years (range 0.5 to 21 years). Patients were excluded if they had a history of squamous cell carcinoma (SCC) at the treatment site. The primary outcome included the proportion of randomized wound pairs with at least 50% healing at month 6 (85% vs 16%, p<0.0001, n=43 wounds per group) and also pain reduction as assessed by the mean difference in patient-reported pain scores (-3.07 vs -0.9, p=0.0002). Secondary outcomes included complete wound healing, defined as re-epithelialization with no drainage or erosion and presence of only minor crusting from baseline at month 3 (14% vs 0%, p=0.0316) and month 6 (16% vs 0%, p=0.0160). The median number of sheets patients received was 6 and the total exposure was 6 months following application. The most common adverse reactions were procedural pain (27%) and pruritis (9%) <a id="