Topical Gene Therapy for Dystrophic Epidermolysis Bullosa Induces Complete Healing

Topical treatment with beremagene geperpavec (B-VEC) was found to promote complete wound healing among patients with dystrophic epidermolysis bullosa, according to the results of a study published in The New England Journal of Medicine.

The topical treatment B-VEC is a herpes simplex virus type 1 (HSV-1)-derived gene therapy that was designed to restore type VII collagen (C7) protein expression that is missing in patients with dystrophic epidermolysis bullosa due to mutations in the collagen type VII alpha 1 chain (COL7A1) gene.

This phase 3, double-blind, placebo-controlled trial was conducted at 3 sites in the United States from 2020 to 2021. Two lesions similar in size and location were identified on 31 patients with dystrophic epidermolysis bullosa, and they were randomly assigned to undergo weekly application of B-VEC or placebo for 26 weeks. The dose of B-VEC ranged between 4×10⁸ and 1.2×10⁹ plaque-forming units, depending on lesion size. The primary efficacy outcome — complete lesion healing at 6 months —  was defined as 100% wound closure at 2 consecutive weeks.

The median age of the patients was 16.1 (range, 1-44) years, 65% were boys or men, 65% were White, and 97% had recessive dystrophic epidermolysis bullosa.

The median area of wounds treated with B-VEC was 10.6 cm² compared with a median area of 10.4 cm² for the placebo-treated wounds.

The proportion of wounds with complete healing at 6 months was 67% for B-VEC treatment compared with 22% for placebo (P =.002).

In addition, B-VEC treatment was associated with significant improvement in pain scores at wound-dressing change compared with placebo at week 22 (adjusted least-squares mean difference [aLSMD], -0.61; 95% CI, -1.10 to -00.13). Treatment with B-VEC tended to be associated with lower pain scores at 24 (aLSMD, -0.88) and 26 (aLSMD, -0.56) weeks compared with placebo.

A total of 45 adverse events were reported during the trial, with 58% of patients experiencing at least 1 event. The most common events were neoplasms (10%), pruritus (10%), and chills (10%). Only 1 event of mild erythema was related to B-VEC treatment. No events led to treatment discontinuation.

At baseline, 64% of patients had HSV-1 antibodies and 5% had C7 antibodies. After 26 weeks of treatment with B-VEC, 75% of patients without HSV-1 antibodies at baseline had seroconversion and 72% of patients without C7 antibodies at baseline had seroconversion. No immunologic reactions were reported.

Response to B-VEC did not depend on HSV-1 serostatus at baseline or C7 seroconversion.

This study may be limited by the fact that the treated lesions were relatively small in size and all but 1 patient had recessive disease.

Study authors concluded, “In this trial involving patients with [dystrophic epidermolysis bullosa], we found that repeated topical application of B-VEC, an HSV-1–based gene therapy, resulted in a greater likelihood of complete wound healing than the topical application of placebo at up to 6 months. Longer and larger trials are warranted to determine the durability of effect and risks of this approach.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.