Life-changing: New gene therapy gel heals decades-old wounds from skin disease

The treatment made a huge difference in the quality of life for trial participants.
Deena Theresa
Gel on beige background stock photo.
Gel on beige background stock photo.

Iryna Mylinska/iStock 

A gene therapy gel for a blistering skin disease developed at Stanford Medicine has worked wonders in a double-blind, placebo-controlled clinical trial.

The gel, called B-VEC, was intended to treat dystrophic epidermolysis bullosa, a skin disease that results in large open wounds that last for decades. The condition is extremely painful, and the medical treatment is mostly limited to palliative care. 

"After four months, I saw an improvement on a large wound on my back that I had for 20 years," said trial participant Vincenzo Mascoli, aged 22, said in a statement. "After six months, the wound had healed completely and was much less painful."

"This was a life-changing event for Vincenzo," said Peter Marinkovich, MD, director of Stanford Medicine's Blistering Disease Clinic and senior author of the study. "Now he can bathe and sleep on his back without pain. This treatment made a huge difference in the quality of life for Vincenzo and other trial participants."

Sixty-seven percent of wounds healed completely in six months

The late-stage trial produced similar results seen in an earlier, smaller trial in nine patients conducted at the Stanford School of Medicine and published in Nature Medicine in March of 2022.

The trial showed improved wound healing in 31 percent with the disease, including 19 who were 18 years old or younger. After six months of weekly applications, 67 percent of wounds healed completely, while only 22 percent of wounds treated with a placebo did so.

Life-changing: New gene therapy gel heals decades-old wounds from skin disease
Representational picture of a woman with allergies.

The therapy gel creates a copy of a missing gene

Patients with recessive dystrophic epidermolysis bullosa have a genetic mutation that hinders them from producing a protein called collagen VII, which is known to bind the middle and outer layers of the skin together. The absence of the protein causes the layers to slide across each other, resulting in blisters that form painful open wounds.

The gel delivers a copy of the collagen VII gene to the surface of the skin. It does so by using a modified herpes simplex virus which, by making the missing protein, stabilizes the skin's structure.

The herpes virus has evolved to evade the human immune system, the release said, so the gel can be applied repeatedly without triggering an immune response.

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"We saw no inflammation, significant side effects, or immune neutralization of the drug, even with repeated administration of the gel over the six months of the trial period," Marinkovich said.

Awaiting FDA approval of the gel

While the previous trial was primarily to demonstrate that gel-treated skin could indeed make collagen VII, the new trial focused on wound healing. "We set a goal for 100 percent healing within six months of treatment. That's a high bar, but we very clearly met the primary objective," said Marinkovich.

Most of the participants continued to receive the gel treatment at home under medical supervision after the trial period ended.

The researchers will also try the gel on patients' hands and mucosal surfaces, including the mouth, throat, eyes, esophagus, and anus.

Marinkovich and his colleagues have applied to the Food and Drug Administration for approval of the gel as a treatment for dystrophic epidermolysis bullosa. Once approved, it would be the first topical gene therapy treatment approved for use in the United States.

 The clinical trial results were published on December 15 in The New England Journal of Medicine.

Study Abstract:

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 ClinicalTrials.gov number, NCT04491604. opens in new tab.)