Vyjuvek for epidermolysis bullosa

Last updated May 24, 2023, by Marisa Horak, MS

 Fact-checked by José Lopes, PhD

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What is Vyjuvek for epidermolysis bullosa?

Vyjuvek (beremagene geperpavec), formerly known as B-VEC, is a gene therapy gel that’s approved for the treatment of wounds in people with dystrophic epidermolysis bullosa (DEB). It is marketed by Krystal Biotech.

The treatment is the first for DEB to be approved by the U.S. Food and Drug Administration (FDA). It also, notably, is the first FDA-approved gene therapy that is designed to be administered more than once.

How does Vyjuvek work?

DEB is caused by mutations in the COL7A1 gene that lead to a deficiency in collagen 7 (COL7), a structural protein that’s important for holding together skin tissue.

Vyjuvek uses a modified and harmless version of the herpes simplex virus to deliver two healthy copies of the COL7A1 gene directly to skin cells in wounds. The delivered gene allows skin cells to produce functional COL7 protein, which increases the skin’s structural integrity, ultimately helping to reduce blistering and resolve wounds.

Who can use Vyjuvek?

Vyjuvek is approved by the FDA to treat wounds in people with DEB, ages 6 months and older, who have mutations in the COL7A1 gene.

Who should not use Vyjuvek?

There are no contraindications for Vyjuvek’s use.

How is Vyjuvek administered?

Vyjuvek is available in a biological suspension, which is mixed with an excipient gel before being applied to the skin. The dosage can be measured in plaque-forming units (PFU, the number of individual virus particles) or in the volume applied (in milliliters or mL).

The gel is applied once per week as droplets over the wound, with each droplet spaced about a centimeter apart from other droplets. The therapy may be applied in a healthcare setting or at home, but the application should always be performed by a healthcare professional.

The recommended dose depends on the size of the wound:

• For wounds less than 20 square cm in size, the recommended dose is 400 million PFU or 0.2 mL.
• For wounds of at least 20 square cm but less than 40 square cm, the dose is 800 million PFU or 0.4 mL.
• For wounds 40 to 60 square cm, the dose is 1.2 billion PFU or 0.6 mL.
• For larger wounds, the dose is calculated by adding 400 million PFU (0.2 mL) for each additional 20 square cm, up to the maximum dose.

For patients younger than age 3, the maximum weekly dose should not exceed 1.6 billion PFU (0.8 mL). For patients ages 3 and older, the maximum weekly dose is 3.2 billion PFU (1.6 mL).

It may not be possible to treat all wounds in a single patient visit. It is recommended that individual wounds be selected and treated until they are closed, before moving on to start treating other wounds. If previously healed wounds re-open, they should be prioritized.

If a dose of Vyjuvek is missed, the next planned dose should be given as soon as possible, with subsequent treatments resuming on a weekly basis after that.

Vyjuvek in clinical trials

The FDA’s approval of Vyjuvek was supported by data from two clinical trials: a Phase 1/2 study called GEM-1, and a Phase 3 trial called GEM-3.

Phase 1/2 GEM-1 trial

The GEM-1 trial (NCT03536143) tested the safety and efficacy of Vyjuvek in six adults and three children who had recessive DEB (RDEB), a more severe subtype of the disease. The adults comprised five men and one woman, while the children in the study were two boys and one girl.

In all participants, one wound was treated with Vyjuvek, while a different wound was administered a placebo. The treatment was generally given along with bandage changes every two or three days, for about three months.

The results showed that wounds given the placebo showed varying amounts of healing or worsening. In comparison, all but one of the wounds treated with Vyjuvek closed completely, and remained healed for at least three months. The only exception, a five-year-old chronic wound on one patient’s foot, closed partly after a month of Vyjuvek treatment, and healed completely upon re-treatment, remaining closed during up to eight months of monitoring.

Phase 3 GEM-3 trial

The GEM-3 study (NCT04491604) enrolled 31 people with DEB, ages 1 to 44. Almost all participants had RDEB; one had the milder dominant form of DEB.

In each participant, one wound was treated with Vyjuvek, while another wound was administered the placebo.

The results showed that, after three months of treatment, significantly more wounds treated with Vyjuvek than placebo had healed (68% vs. 23%). A similar difference was seen after six months of treatment (65% vs. 26%), meeting the study’s main goal.

Participants who completed the GEM-3 trial, as well as certain patients who were not able to participate in the initial study, had the option to join an open-label extension study (NCT04917874). In that part, all are being treated with Vyjuvek and monitored for up to about two years. The extension study is ongoing at several U.S. centers.

Common side effects of Vyjuvek

The most common side effects of Vyjuvek include:

• itching
• chills
• redness
• rash
• cough
• runny nose.

Accidental exposure

The modified herpes virus contained in Vyjuvek cannot replicate in human cells, and it doesn’t alter a cell’s DNA. Still, as a precaution, it’s recommended to avoid contact with the therapy except as directed for treatment.

After Vyjuvek is applied, it’s recommended that patients avoid touching or scratching the wound or having contact with its dressings for at least 24 hours. When changing wound dressings that have been in direct contact with the therapy, protective gloves should be worn.

In the event of an accidental exposure — for example, if the therapy is splashed to the eye or a mucous membrane — the exposed area should be thoroughly washed for at least 15 minutes.

Use in pregnancy and breastfeeding

There is no available data on the use of Vyjuvek in people who are pregnant or breastfeeding, and animal studies have not been conducted. It’s recommended that patients who can become pregnant should use an effective form of birth control to avoid pregnancy while being treated with Vyjuvek.