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.

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.