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

Abstract

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 × 10⁹ 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.

Keywords: B‐VEC; Japan; clinical trial; dystrophic epidermolysis bullosa; topical therapy.

FIGURE 1

Primary wound closure assessments at baseline, Month 3 (Weeks 8, 10, and 12), Month 6 (Weeks 22, 24, and 26), Month 9 (Weeks 36, 38, and 40), Month 12 (Weeks 48, 50, and 52), and the SFU visit (90 ± 7 days after last dose) for the four subjects that completed the study. Wounds were assessed for 100% complete wound closure, specified as skin re‐epithelialization without drainage, as determined live by the investigator. SFU, safety follow‐up.

FIGURE 2

Primary wound images at baseline, Week 12 (Month 3), and Week 26 (Month 6) for the four subjects that completed the study.

FIGURE 3

Number of treatment‐emergent adverse events (TEAEs) by severity and the number of unique subjects experiencing each TEAE.

FIGURE 4

Patient‐reported outcome measures at specific visits during the study. Mean and individual scores are presented at baseline (yellow), Week 26 (green), Week 38 (red), and Week 52 (blue). TSQM‐9 treatment satisfaction is presented for the three domains assessed (Convenience, Effectiveness, and Global Satisfaction) at (a) Week 26 and (b) Week 52. Skindex‐29 (skin‐specific quality‐of‐life) is presented for the (c) Emotions, (d) Functioning, and (e) Symptoms domains. The (f) VAS Pain (severity of pain associated with Primary Wound dressing changes) and (g) EQ VAS (general health status) are presented by visit. EQ VAS, EuroQol visual analog scale; TSQM‐9, Treatment Satisfaction Questionnaire for Medication 9; VAS, visual analog scale.