Double dose of Vyjuvek safely heals extensive wounds in woman with RDEB
Temporary increase of gene therapy may 'offer meaningful clinical benefit': Report
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Doubling the standard dose of the gene therapy Vyjuvek (beremagene geperpavec) successfully healed widespread wounds in a woman with recessive dystrophic epidermolysis bullosa (RDEB) without causing side effects, a new case report shows.
While the topical gel is already approved in the U.S. to treat the disease, the standard weekly dose is often not enough to cover every wound on patients with extensive skin damage. By using an off-label, double-dose approach for six months, the woman was able to treat wounds covering half of her body, significantly reducing her pain and clearing the majority of her new blisters.
“This report highlights the potential therapeutic benefit of [Vyjuvek] at increased doses, as patients with RDEB are limited by the standard prescribed volume when managing extensive wound burden,” researchers wrote.
The study, “Off‐Label Use of Double‐Dose Beremagene Geperpavec (B‐VEC) in the Treatment of Recessive Dystrophic Epidermolysis Bullosa: A Promising Clinical Case,” was published in Pediatric Dermatology.
The challenge of limited dosing in RDEB
DEB is a type of epidermolysis bullosa, a group of diseases in which the skin is fragile and wounds easily. Mutations in the COL7A1 gene, which contains instructions for cells to manufacture part of the type VII collagen protein, cause DEB. Type VII collagen typically helps connect different layers of the skin. Its loss can lead to the layers separating, resulting in blistering after very small injuries.
Individuals can inherit DEB in either a recessive pattern, where they require two mutated copies of COL7A1, or a dominant pattern, where they require only one mutated copy for the disease to develop.
Vyjuvek is a gene therapy gel that can help treat wounds in DEB. It delivers healthy copies of COL7A1 to skin cells in wounds, allowing them to produce functional type VII collagen.
Approvals by the U.S. Food and Drug Administration (FDA) allow people with DEB who are at least 3 years old to use up to 1.6 mL weekly (3.2 billion PFU, or plaque-forming units). This dose “has demonstrated promising results in wound healing for patients with DEB,” the researchers wrote. “However, the current FDA-approved prescribing volume limits the number of wounds patients can treat in a weekly application.”
In the new report, they describe a case in which a woman with recessive DEB required a higher dosage of Vyjuvek. The 26-year-old woman initially had wounds covering about 15% to 20% of her body. As a result, she began using the medication at the maximum approved dose.
“Within a few weeks of starting treatment, she reported significant improvement in her wounds, particularly on her legs, with near complete healing of most treated areas,” the researchers wrote.
However, six months later, she developed acute urticaria (hives) after taking an antibiotic for a urinary tract infection. Her scratching triggered new blisters, resulting in wounds covering about half of her body. She rated her pain at an 8 out of 10.
The standard Vyjuvek prescription wasn’t able to cover all of her new, active wounds. To address this issue, her clinicians requested insurance approval for off-label doubling of the weekly dose to 3.2 mL. The insurance provider approved this increase for a six-month period. At this dose, she could apply the therapy to all of her wounds each week.
Successful healing with double doses
Five months later, many of the wounds had resolved. This meant active wounds once again covered about 15% to 20% of her skin. She also reported a decrease in pain, rating it at 3 out of 10. No side effects were reported.
After six months on the higher dose, the woman returned to her standard weekly dose of 1.6 mL.
“Our patient tolerated a temporary doubling of the weekly [Vyjuvek] dose without any adverse events and experienced notable clinical improvement,” the researchers wrote. “This suggests that, for select patients with wound burden exceeding standard dosing capacity, a temporary dose escalation of [Vyjuvek] may safely offer meaningful clinical benefit.”
In addition, the case suggests that the gene therapy may be more effective in treating acute wounds compared to chronic wounds, as they have different inflammatory states and microbial populations, the team noted.
“Additional studies are needed to investigate treatment outcomes since many RDEB patients may benefit from long-term coverage of increased doses of [Vyjuvek],” the team wrote.
