Topical gene therapy for severe recessive dystrophic epidermolysis bullosa: clinical outcomes and multidisciplinary management in three patients treated with beremagene geperpavec (B-VEC) in Italy - a case series.

内容摘要

Recessive dystrophic epidermolysis bullosa is a severe inherited blistering disorder characterized by chronic wounds, fibrosis and systemic complications. Beremagene geperpavec (B-VEC), a topical HSV1-based gene therapy delivering full-length COL7A1, has shown efficacy in clinical trials; however, real-world data remain limited. This retrospective, descriptive case series reports on three patients with genetically confirmed recessive dystrophic epidermolysis bullosa - two children and one young adult - treated between 2024 and 2026 at two Italian tertiary centres. All patients had extensive chronic skin involvement and received weekly topical B-VEC. Clinical data included wound characteristics, response to therapy, supportive care and adverse events. All patients showed clinically meaningful improvement in target wound healing. One child achieved ~70% reduction in the wound area needing treatment; the second had ~50% with shallower morphology and reduced bleeding. The adult, previously enrolled in the GEM-3 trial, achieved over 60% wound closure after reinitiating B-VEC via Italy's 5% Italian Medicines Agency (AIFA) access programme. No treatment-related adverse events occurred. Adjunctive care included wound hygiene optimization, nutritional and iron support, and pain control. In this small descriptive case series, B-VEC was well tolerated and associated with clinically meaningful improvement in wound healing though outcomes were more variable and, in some cases, less pronounced than those reported in pivotal trials, nevertheless supporting its integration into a comprehensive care model that addresses infection risk, anaemia, nutrition, and wound management. Recessive dystrophic epidermolysis bullosa (RDEB) is a rare and severe inherited skin disease. People with RDEB have very fragile skin that blisters and tears easily, even with minor friction or everyday activities. This happens because they lack a protein called type VII collagen, which normally helps anchor the outer layer of the skin to the layer underneath. Without this protein, the skin is unstable and wounds form easily. Children and adults with RDEB often live with chronic (long-lasting) open wounds that may take weeks, months or even years to heal. These wounds can be painful, bleed frequently and become infected. Over time, repeated cycles of injury and scarring can lead to complications such as joint stiffness, fusion of fingers or toes, difficulty swallowing, anaemia, malnutrition, and an increased risk of a serious type of skin cancer. Daily wound care can take several hours and places a heavy physical and emotional burden on patients and caregivers. Until recently, treatment for RDEB focused only on managing symptoms, that is, protecting the skin, preventing infections, controlling pain and providing nutritional support. However, a new therapy called beremagene geperpavec (B-VEC) has been developed to address the underlying genetic cause of the disease. B-VEC is a topical (applied directly to the skin) gene therapy. It uses a modified, non-replicating virus to deliver a healthy copy of the COL7A1 gene to skin cells. This gene allows the cells to produce type VII collagen, helping the skin repair itself. In this report, we describe the cases of three patients with severe RDEB — two children and one young adult — treated with weekly applications of B-VEC at two specialized hospitals in Italy. All patients had large areas of chronic wounds and significant complications related to their disease. After starting B-VEC treatment, all three patients showed clear improvement in the treated wounds. The size of the main target wounds decreased by approximately 50–70%. The wounds became shallower, less inflamed and less prone to bleeding. In the adult patient, some areas of the back that had healed during earlier clinical trial participation remained closed up to the last hospital visit. Although some wounds, especially in areas exposed to pressure, such as the thigh in a wheelchair user, reopened over time, they often healed again more quickly with continued treatment. Importantly, no treatment-related serious side effects were observed. The therapy was well tolerated in both children and the adult patient. Our experience also highlights that gene therapy works best when combined with comprehensive care. All patients continued to receive careful wound cleaning and dressing, nutritional support, iron supplementation or blood transfusions when needed, and pain management. Addressing these factors is essential because poor nutrition, anaemia and infections can slow wound healing. In summary, this real-world experience supports the safety and effectiveness of B-VEC for people with severe RDEB. While it is not a cure, it represents an important step forward. When integrated into a multidisciplinary care approach, B-VEC may enhance durable wound closure, thereby reducing wound burden, improving quality of life, and helping patients better manage this challenging condition.