Dystrophic Epidermolysis Bullosa: Positive Results from Topical Gene Therapy

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Recent trial data showed positive results for B-VEC topical gene therapy treatment for dystrophic epidermolysis bullosa patients.

Dystrophic epidermolysis bullosa patients saw 70% of their wounds show complete closure after 6 months of topical gene therapy known as beremagene geperpavec (B-VEC), according to new research.

A rare genetic skin disorder, dystrophic epidermolysis bullosa results from mutations in the COL7A1 gene, causing patients to suffer from extreme skin fragility prone to everyday traumas from even small touches.

B-VEC therapy was developed by modifying a herpes simplex virus type 1 (HSV-1) vector, within which 2 copies of the COL7A1 coding sequence were placed. The gene delivery system transcribes this viral DNA, translating it into C7 leading to secretion into the extracellular space.

The research’s summary was written by Aimee S. Payne, MD, PhD, from University of Pennsylvania, Philadelphia’s Center for Cellular Immunotherapies. The study summarized was led by Shireen Guide, MD, from the Children’s Hospital of Orange County, California, and Isin Sinem Bağcı, MD, from Stanford School of Medicine.

“The HSV-1 viral genome does not permanently integrate into host DNA — it is diluted with each cell division,” Payne wrote. “Therefore, the therapeutic effects of B-VEC are transient, and for long-term disease control, repetitive administration would be required.”


Researchers developed B-VEC therapy by modifying an HSV-1 vector, encapsulating 2 COL7A1 coding sequence copies.

This gene delivery system works by transcribing this viral DNA and then translating it into C7 protein, which leads to secretion outside of the cell membrane and builds up the anchoring fibrils of the skin.

The modifications made to the HSV-1 vector modifications limit hosts’ inflammatory responses, in addition to preventing the usual viral replication of HSV-1.

Repeated administration of this therapy is necessary, as the viral genome does not integrate into its host’s DNA permanently due to the dilution that occurs through each cell division.

Following phase 1 and 2 trials of the new topical gene therapy, a new phase 3, randomized, double-blind, placebo-controlled trial was conducted.

The trial assessed the data of 31 dystrophic epidermolysis bullosa patients, including 1 patient with the dominant form of the condition and 30 with the recessive.

Study Findings

The results of the phase 3 trial demonstrated that about 70% of the wounds of 31 dystrophic epidermolysis bullosa patients closed by 6 months, including the single patient with the dominant form of the condition.

The reported 70% wound closure rate was compared to those in the placebo arm of the study, whose rate of closure was only about 20%.

The investigators also noted that patients given B-VEC therapy showed 50% wound healing durability, which was defined by the team as complete closure by both 3 months and 6 months. This was compared to only 7% of those given the placebo.

“In a previous phase 1–2 study, electron microscopy of skin biopsy samples obtained from patients with recessive dystrophic epidermolysis bullosa showed that B-VEC restored C7 expression on immunofluorescence staining at the basement-membrane zone and induced formation of anchoring fibrils,” Payne wrote. “Thus, topical gene therapy with B-VEC reverses the histopathological and ultrastructural abnormalities in the skin of patients with dystrophic epidermolysis bullosa.”

The article, “Topical Gene Therapy for Epidermolysis Bullosa,” was published online by the New England Journal of Medicine.