Trial of Beremagene Geperpavec (B-VEC) for Dystrophic Epidermolysis Bullosa

N Engl J Med. 2022 Dec 15;387(24):2211-2219. doi: 10.1056/NEJMoa2206663.


Background: Dystrophic epidermolysis bullosa is a rare genetic blistering skin disease caused by mutations in COL7A1, which encodes type VII collagen (C7). Beremagene geperpavec (B-VEC) is a topical investigational herpes simplex virus type 1 (HSV-1)-based gene therapy designed to restore C7 protein by delivering COL7A1.

Methods: We conducted a phase 3, double-blind, intrapatient randomized, placebo-controlled trial involving patients 6 months of age or older with genetically confirmed dystrophic epidermolysis bullosa. For each patient, a primary wound pair was selected, with the wounds matched according to size, region, and appearance. The wounds within each pair were randomly assigned in a 1:1 ratio to receive weekly application of either B-VEC or placebo for 26 weeks. The primary end point was complete wound healing of treated as compared with untreated wounds at 6 months. Secondary end points included complete wound healing at 3 months and the change from baseline to weeks 22, 24, and 26 in pain severity during changes in wound dressing, assessed with the use of a visual analogue scale (scores range from 0 to 10, with higher scores indicating greater pain).

Results: Primary wound pairs were exposed to B-VEC and placebo in 31 patients. At 6 months, complete wound healing occurred in 67% of the wounds exposed to B-VEC as compared with 22% of those exposed to placebo (difference, 46 percentage points; 95% confidence interval [CI], 24 to 68; P = 0.002). Complete wound healing at 3 months occurred in 71% of the wounds exposed to B-VEC as compared with 20% of those exposed to placebo (difference, 51 percentage points; 95% CI, 29 to 73; P<0.001). The mean change from baseline to week 22 in pain severity during wound-dressing changes was -0.88 with B-VEC and -0.71 with placebo (adjusted least-squares mean difference, -0.61; 95% CI, -1.10 to -0.13); similar mean changes were observed at weeks 24 and 26. Adverse events with B-VEC and placebo included pruritus and chills.

Conclusions: Complete wound healing at 3 and 6 months in patients with dystrophic epidermolysis bullosa was more likely with topical administration of B-VEC than with placebo. Pruritus and mild systemic side effects were observed in patients treated with B-VEC. Longer and larger trials are warranted to determine the durability and side effects of B-VEC for this disease. (Funded by Krystal Biotech; GEM-3 number, NCT04491604.).

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Topical
  • Collagen Type VII* / administration & dosage
  • Collagen Type VII* / adverse effects
  • Collagen Type VII* / genetics
  • Collagen Type VII* / metabolism
  • Epidermolysis Bullosa Dystrophica* / drug therapy
  • Epidermolysis Bullosa Dystrophica* / genetics
  • Epidermolysis Bullosa Dystrophica* / metabolism
  • Genetic Therapy* / adverse effects
  • Genetic Therapy* / methods
  • Humans
  • Pruritus / chemically induced
  • Wound Healing / drug effects
  • Wound Healing / genetics


  • COL7A1 protein, human
  • Collagen Type VII

Associated data