Efficacy and Safety of the Topical Gene Therapy Beremagene Geperpavec-svdt (B-VEC) in an Open-Label Study of Japanese Subjects With Dystrophic Epidermolysis Bullosa

Dystrophic epidermolysis bullosa (DEB) patients have pathogenic variants in COL7A1, leading to skin fragility, blistering, and scarring. Beremagene geperpavec-svdt (B-VEC) is a replication-defective herpes simplex virus type 1 (HSV-1)-based gene therapy vector administered topically to deliver functional COL7A1 to DEB wounds. In a United States (US) Phase 3 study, B-VEC significantly improved wound healing at 3 and 6 months compared to placebo, and in a US open-label extension (OLE) study, weekly B-VEC administration was well tolerated for up to 112 weeks. The present study was conducted to confirm the efficacy and safety of B-VEC in a cohort of Japanese DEB patients receiving weekly B-VEC treatment (4.0 x 10(9) plaque forming units (PFU)/mL) for 52 weeks. Wound healing assessments were conducted on a Primary Wound at visits corresponding to Month 3 (the secondary efficacy endpoint), Month 6 (the primary efficacy endpoint), and Months 9 and 12 (exploratory durability endpoints). Patient-reported outcome (PRO) measures were employed as exploratory analyses of efficacy. Safety was assessed by adverse events (AEs) and clinical laboratory tests. Five subjects enrolled in the study; one discontinued due to challenges with following wound dressing disposal guidelines. The study met its primary and secondary efficacy endpoints with 100% of Primary Wounds demonstrating complete closure at Months 6 and 3, respectively; durable complete closure was observed in 3/4 (75%) of wounds at Months 9 and 12. PROs indicated decreased pain, improvement in skin-specific quality of life, and moderate to high treatment satisfaction. Four subjects reported ten AEs; all were assessed as mild or moderate in severity and unrelated to treatment by Investigators. None were serious, severe, or led to treatment/study discontinuation. The results of the Japan OLE study are in agreement with the US Phase 3 and OLE studies, demonstrating the efficacy and safety of B-VEC in Japanese patients with DEB. Trial Registration: Japan Registry of Clinical Trials: jRCT2053230075