Beremagen geperpavec

Beremagen geperpavec (Vyjuvek) is a non-integrating and non-replicating herpes simplex virus vector that expresses functional collagen type V- II in wound cells and thus promotes wound healing. In wounds treated locally with beremagen, the gene COL7A1 enables the synthesis of collagen type VII in keratinocytes and fibroblasts (Guide SV et al. 2022).

Beremagen geperpavec (Vyjuvek) is the first topical corrective gene therapy available for patients with epidermolysis bullosa dystrophica with COL7A1 mutations. The therapy is approved from birth for weekly application to wounds.

The active ingredient Beremagen geperpavec is a genetically engineered herpes simplex virus type 1 (HSV-1) vector carrying the human COL7A1 gene. This vector encodes two copies of the complete human COL7A1 gene and restores the COL7 protein after topical application to DEB wounds. This restores the production of functional collagen type VII in infected keratinocytes and fibroblasts. This collagen forms anchoring fibrils between the epidermis and dermis and thus contributes to the restoration of skin integrity.

The efficacy of Beremagen geperpavec (Vyjuvek) was investigated in a randomized, placebo-controlled phase III study with 31 patients (20 male, 11 female) aged 1 to 44 years. All subjects had one or more genetically confirmed mutations in the COL7A1 gene, including 30 with autosomal recessive and one patient with autosomal dominant DEB.

For each participant, two comparable wounds were selected, randomized and treated cutaneously with either Beremagen geperpavec or placebo (gel only) once a week for a period of 26 weeks. The maximum total weekly dose was based on age category:

• ≥ 6 months to < 3 years: 1.6 × 10⁹ PFU/week
• ≥ 3 years to < 6 years: 2.4 × 10⁹ PFU/week
• ≥ 6 years: 3.2 × 10⁹ PFU/week

The primary endpoint was improved wound healing, defined as the difference in the proportion of complete (100%) wound closures after 24 weeks between the wounds treated with Beremagen geperpavec and those treated with placebo. Complete wound closure had to be confirmed at two consecutive study visits two weeks apart at weeks 22 and 24 or at weeks 24 and 26 (Marinkovich MP et al. 2025 /Natsuga K et al. 2025).

Vyjuvek is indicated for the treatment of wounds in patients from birth with dystrophic epidermolysis bullosa and proven mutation(s) in the gene for the alpha-1 chain of collagen type VII(COL7A1).

Vyjuvek is contraindicated in:

• hypersensitivity to beremagen geperpavec or any of the other ingredients of the medicinal product
• pregnant women
• Vyjuvek must not be used on wounds diagnosed or suspected of having squamous cell carcinoma (SCC); however, treatment of other, unaffected wounds is possible.

Precautions before handling and use:

• Vyjuvek contains genetically modified organisms. Appropriate safety precautions should be taken during preparation, use and disposal. Personal protective equipment such as gloves, mask and eye protection must be worn when handling the preparation.
• Pregnant women must not prepare or apply the medicinal product and should avoid any direct contact with treated wounds or the associated dressings.

Pregnancy: No data are available on the use of Beremagen geperpavec in pregnant women. Animal studies on reproductive toxicity are available but are not sufficient to assess potential risks. For this reason, the use of Vyjuvek during pregnancy is not recommended.

Lactation: It is not known whether beremagen geperpavec passes into human breast milk. A risk for newborns and infants cannot be excluded. It should be decided on an individual basis whether breastfeeding should be discontinued or whether treatment with Vyjuvek should be discontinued. The benefits of breastfeeding for the child and the benefits of the therapy for the mother must be carefully weighed against each other.

In children < 3 years of age, the recommended maximum total weekly dose is 1 ml, corresponding to 2 × 10⁹ plaque-forming units (PFU).

In children aged 3 years and older, adolescents and adults, the recommended maximum total weekly dose is 2 ml, corresponding to 4 × 10⁹ PFU.

Beremagen geperpavec is intended exclusively for local application to open lesions. Before use, the suspension and gel must be thawed and mixed into a gel in the pharmacy. Special precautions must be taken during preparation, application and disposal as this is a medicinal product containing genetically modified organisms.Beremagen geperpavec is applied to the wounds to be treated once a week in small drops at a distance of about 1 cm. The treatment is continued until the wounds are closed. Wounds that have already been treated and reopened should be given priority in the weekly application. Application should not take place if open lesions are present.

Beremagen geperpavec should be applied by healthcare professionals in a medical setting, such as a clinic, or in the home. If medically acceptable, it can also be applied by the patient or by a trained caregiver. The gel is applied in a grid pattern. After application, the wound is covered with a hydrophobic dressing, which is then secured with a standard dressing. The dressing should remain on the wound for about 24 hours. The usual standard care can then be continued.

The dosage depends on the wound area:

• For a wound area of < 20 cm², the volume is < 0.2 ml.
• For a wound area of 20 to < 40 cm², the volume is 0.2 to < 0.4 ml.
• For a wound area of 40 to < 60 cm², the volume is 0.4 to < 0.6 ml.
• For a wound area of 60 to < 200 cm², the volume is 0.6 to < 2 ml.

Treatment is continued weekly until the wound is completely closed. In case of recurrence in loco, a new application can be carried out. If there are no wounds, Vyjuvek must not be used.

The following information is based on the adverse reactions observed in the pivotal clinical trial. In this study, 58% of patients reported at least one adverse reaction. None of the side effects reported led to discontinuation of treatment.

The most frequently reported side effects were:

• chills (9.7 %) and
• itching (9.7 %).

Other common side effects:

• cough
• rhinorrhea
• erythema
• skin rash

No interaction studies have been carried out for Beremagen geperpavec. However, no other topical medicinal products should be applied simultaneously to wounds treated with Vyjuvek.

The safety of vaccination with live viral vaccines during or after treatment has not been investigated. However, it is considered unlikely that Vyjuvek will interfere with the immune response to such vaccines.

To ensure the traceability of biological medicinal products, both the name of the medicinal product and the batch number must be clearly documented.

Transmission of infectious agents: Although Beremagen geperpavec is not replicated in cells and is not integrated into DNA, there is some risk of transmission of infectious agents despite sterility testing. Therefore, patients should be monitored for signs of infection after treatment and treated if necessary. Persons handling Vyjuvek or assisting with dressing changes must wear protective equipment.

Hygiene measures and patient education: Caregivers or healthcare professionals applying the gel must ensure that treated wounds are properly covered with dressings. Patients should be instructed not to touch or scratch treated wound areas to avoid contamination of other areas of the body or transmission during close contact.

Long-term follow-up: For long-term follow-up, patients are expected to participate in a non-interventional, multicenter study to evaluate the safety of Vyjuvek under real-life conditions.

1. Dellambra E et al. (1998) Corrective transduction of human epidermal stem cells in laminin-5-dependent junctional epidermolysis bullosa. Hum Gene Ther 9:1359-1370.
2. De Rosa L et al. (2022) The joint battle to tackle epidermolysis bullosa through gene therapy. Trends Mol Med 28:533-535.
3. Dhillon S (2024) . Beremagene Geperpavec: First Approval. Drugs. 2023 Aug;83(12):1131-1135.
4. Epstein AL et al. (2023) Herpes simplex virus gene therapy for dystrophic epidermolysis bullosa (DEB). Cell 186:3523-3523.e1.
5. Guide SV et al. (2022) Trial of Beremagene Geperpavec (B-VEC) for Dystrophic Epidermolysis Bullosa. N Engl J Med 387:2211-2219.
6. Gurevich I et al. (2023) In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial. Nat Med 28:780-788.
7. Hirsch T. (2017) Regeneration of the entire human epidermis using transgenic stem cells. Nature 551:327-332
8. Marinkovich MP et al. (2025) Long-Term Safety and Tolerability of Beremagene Geperpavec-svdt (B-VEC) in an Open-Label Extension Study of Patients with Dystrophic Epidermolysis Bullosa. Am J Clin Dermatol 26:623-635.
9. Mavilio F et al. (2006) Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells. Nat Med 12:1397-402.
10. Mavilio F (2006) Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells. Nat Med 12:1397-1402.
11. Natsuga K et al. (2025) Efficacy and Safety of the Topical Gene Therapy Beremagene Geperpavec-svdt (B-VEC) in an Open-Label Study of Japanese Subjects With Dystrophic Epidermolysis Bullosa. J Dermatol 52:1494-1502.
12. Paller AS et al. (2024) Practical considerations relevant to treatment with the gene therapy beremagene geperpavec-svdt for dystrophic epidermolysis bullosa. J Dermatolog Treat 35:2350232.
13. Vailly J et al. (1998) Corrective gene transfer of keratinocytes from patients with junctional epidermolysis bullosa restores assembly of hemidesmosomes in reconstructed epithelia. Gene Ther 5:1322-1332.