Description

Beremagene geperpavec-svdt (e.g., Vyjuvek) is a topically applied, redosable, live, replication defective herpes simplex virus-1 (HSV-1) vector -based gene therapy, that delivers functional human collagen type VII alpha 1 chain (COL7A1) genes in individuals with both, dominant and recessive dystrophic epidermolysis bullosa. Beremagene geperpavec (B-VEC) can transduce both keratinocytes and fibroblasts and restore functional COL7 protein. It received its first approval in the United States for the treatment of wounds in individuals with dystrophic epidermolysis bullosa (DEB) with mutation(s) of the COL7A1 gene.

Upon topical application to the wounds, B-VEC can transduce both keratinocytes and fibroblasts. Following the delivery of B-VEC into the cells, the vector genome enters the nucleus. Once in the nucleus, transcription of the encoded human COL7A1 is initiated, without the integration of the vector into the human genome. The resulting transcripts allow production and secretion of mature COL7 protein. These COL7 proteins arrange into bundles of long, thin anchoring fibrils that hold the epidermis and dermis together and are essential for maintaining the integrity of the skin. Individuals with DDEB have fewer normal functional anchoring fibrils, and individuals with RDEB have no functional anchoring fibrils.

Epidermolysis bullosa (EB) is a rare, inherited connective tissue disorder characterized by abnormalities in cohesion of the layers of the skin that can result in blisters, erosions, nonhealing ulceration, and scars in response to trauma or friction. DEB is caused by mutations in the COL7A1 gene that lead to dysfunctional type VII collagen protein, which normally binds the dermal and epidermal layers of the skin. The U.S. prevalence of DEB is estimated to be about 3.26 per million people (which calculates to approximately 1,100 individuals). However, DEB is underdiagnosed, and it is estimated that there are currently 3,000 U.S. individuals living with DEB.

There are two main types of DEB based on the inheritance pattern: recessive dystrophic epidermolysis bullosa (RDEB) and dominant dystrophic epidermolysis bullosa (DDEB). B-VEC is approved to treat both conditions.

Recessive DEB (RDEB) is generally the more severe form. Infants with RDEB typically have widespread blistering and areas of missing skin. As blisters heal, they result in severe scarring, which can cause additional complications. Scarring and blisters in the mouth and esophagus can make it difficult to chew and swallow food, leading to chronic malnutrition and slow growth. Ongoing scarring and fibrosis can lead to fusion of the skin between the fingers and toes (pseudosyndactyly), loss of fingernails and toenails, joint deformities that restrict movement (contractures), and eye inflammation and ulceration leading to vision loss. Early onset of aggressive squamous cell carcinomas (SCCs) at chronic wound sites is typical of RDEB and represents the major cause of death. A systematic review found that in severe RDEB, the risk of SCC was 76% and mortality from SCC reached 84% by 40 years of age (Orphanet Journal of Rare Diseases, 2021).

Dominant DEB (DDEB) is considered the milder form, although its severity is variable. Blisters may be present at birth, but typically appear during early childhood and tend to occur at vulnerable sites such as knees, ankles, elbows, and knuckles. In adulthood, they usually become less frequent and scars fade. Other signs and symptoms of DDEB may include absent fingernails and toenails, constipation, dental caries, and issues with swallowing. Mild cases of DEB are often not fatal, and individuals have a normal life expectancy. However, individuals with severe disease have a life expectancy that ranges from infancy to about 30 – 40 years of age.

Policy

Vyjuvek is proven and MEDICALLY NECESSARY for the treatment of wounds in patients with dystrophic epidermolysis bullosa (DEB) who meet all of the following criteria:

• Patient is aged at least 6 months and older; and
• Diagnosis of dystrophic epidermolysis bullosa (DEB); and
• Submission of medical records (e.g., chart notes, laboratory values) confirming a mutation in the collagen type VII alpha 1 chain (COL7A1) gene; and
• Patient has at least one recurrent or chronic open wound that meets all the following criteria:
  • Adequate granulation tissue
  • Excellent vascularization
  • No evidence of active wound infection
  • No evidence or history of squamous cell carcinoma
• Vyjuvek is prescribed by, or in consultation with, a dermatologist with expertise in the treatment of DEB; and
• Dosing is in accordance with the United States Food and Drug Administration approved labeling.

Initial authorization will be issued for no more than 6 months and no more than 26 doses.

For continuation of therapy, all of the following:

• Patient has previously been treated with Vyjuvek therapy;
• Patient had a positive clinical response to Vyjuvek therapy (e.g., decrease in wound size, increase in granulation tissue, complete wound closure); and
• Wound(s) being treated to meet all of the same criteria for initial approval.

Reauthorization will be issued for no more than 6 months and no more than 26 doses

References

1. Vyjuvek [package insert]. Pittsburgh, PA: Krystal Biotech, Inc.; 2023
2. Bruckner, A.L., Losow, M., Wisk, J. et al.(2020) The challenges of living with and managing epidermolysis bullosa: insights from patients and caregivers. Orphanet J Rare Dis 15, 1 (2020). https://doi.org/10.1186/s13023-019-1279-y
3. Feinstein, J.A., Bruckner, A.L., Chastek, B. et al.(2022) Clinical characteristics, healthcare use, and annual costs among patients with dystrophic epidermolysis bullosa. Orphanet J Rare Dis 17, 367 (2022). https://doi.org/10.1186/s13023-022-02509-0
4. Fine JD.(2016) Epidemiology of Inherited Epidermolysis Bullosa Based on Incidence and Prevalence Estimates from the National Epidermolysis Bullosa Registry. JAMA Dermatol. Nov 01 2016; 152(11): 1231-1238. PMID 27463098
5. Guide SV, Gonzalez ME, Bagci IS, et al.(2022) Trial of Beremagene Geperpavec (B-VEC) for Dystrophic Epidermolysis Bullosa. N Engl J Med. Dec 15 2022; 387(24): 2211-2219. PMID 36516090
6. Has C, Bauer JW, Bodemer C, et al.(2020) Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility. Br J Dermatol. Oct 2020; 183(4): 614-627. PMID 32017015
7. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc. Accessed Jul 26, 2023.
8. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Accessed Jul 26, 2023.
9. Mellerio JE, Hachem ME, Bellon N et al. Emergency management in epidermolysis bullosa: consensus clinical recommendations from the European reference network for rare skin diseases. Orphanet Journal of Rare Diseases. 2020; 15(142): 1-10.
10. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2023 [cited Jul 26, 2023]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.
11. Wounds International consensus guidelines: Skin and wound care in epidermolysis bullosa. 2017. Available at af13d6_01ed147ab87e49c584c20a917c47f19f.pdf (usrfiles.com).

Coding Section

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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