Long-Term Safety and Tolerability of Beremagene Geperpavec-svdt (B-VEC) in an Open-Label Extension Study of Patients with Dystrophic Epidermolysis Bullosa

• Published in: American journal of clinical dermatology Vol. 26; no. 4; pp. 623 - 635
• Main Authors: Marinkovich, M. Peter, Paller, Amy S., Guide, Shireen V., Gonzalez, Mercedes E., Lucky, Anne W., Bağcı, Işın Sinem, Agostini, Brittani, Fitzgerald, Kolleen, Chen, Shijie, Chen, Hubert, Conner, Meghan M., Krishnan, Suma M.
• Format: Journal Article
• Language: English
• Published: New Zealand Springer Nature B.V 01.07.2025; Springer International Publishing
• Subjects: Adolescent; Adult; Child; Clinical outcomes; Collagen Type VII - genetics; Epidermolysis Bullosa Dystrophica - genetics; Epidermolysis Bullosa Dystrophica - therapy; FDA approval; Female; Gene therapy; Genetic Therapy - adverse effects; Genetic Therapy - methods; Genetic Vectors - administration & dosage; Genetic Vectors - adverse effects; Herpes viruses; Herpesvirus 1, Human - genetics; Humans; Hypothesis testing; Male; Middle Aged; Original; Patient Reported Outcome Measures; Patient satisfaction; Patient Satisfaction - statistics & numerical data; Quality of Life; Questionnaires; Skin; Skin - pathology; Time Factors; Treatment Outcome; Wound healing; Wound Healing - genetics; Young Adult; United States > US
• ISSN: 1175-0561; 1179-1888; 1179-1888
• DOI: 10.1007/s40257-025-00942-y

Patients with dystrophic epidermolysis bullosa have pathogenic variants in COL7A1, leading to skin fragility. Beremagene geperpavec-svdt (B-VEC) is a modified, herpes simplex virus type 1-based gene therapy vector that topically delivers COL7A1 to dystrophic epidermolysis bullosa wounds. In a phase III study, B-VEC significantly improved wound healing at 3 and 6 months compared with placebo. We aimed to evaluate the safety and tolerability of B-VEC beyond 6 months in patients with dystrophic epidermolysis bullosa. An open-label extension study was conducted with 47 subjects (24 rollover from phase III; 23 treatment naïve) receiving B-VEC weekly to target wound areas for up to 112 weeks (median 81 weeks). Safety was assessed by adverse events. Treatment satisfaction and quality of life were assessed with patient-reported outcomes as exploratory measures of efficacy. Selected wounds from phase III rollover subjects were assessed for closure. Thirty-five subjects (74.5%) reported one or more adverse events; most were mild or moderate in severity. Fourteen subjects experienced 17 serious adverse events and ten experienced 14 severe adverse events; none was considered treatment related. No adverse events led to treatment or study discontinuation. Patient-reported outcomes indicated high levels of treatment satisfaction, but were inconclusive with regard to quality of life. Among rollover subjects, wounds that received B-VEC during phase III maintained high closure rates during the open-label extension (range 61.1-89.5%, assessed baseline to month 12). This was an open-label design, with a variable follow-up. Patients undergoing extended B-VEC treatment maintained high satisfaction and continued to respond to treatment with no new safety signals detected in the open-label extension study, supporting the continuous use of B-VEC. NCT04917874 (date of trial registration: 8 June, 2021).