Prademagene Zamikeracel (Zevaskyn)

Number: 1084

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses prademagene zamikeracel (Zevaskyn) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of prademagene zamikeracel (Zevaskyn) is required of all Aetna participating providers and members in applicable plan designs. For precertification of prademagene zamikeracel (Zevaskyn), call (866) 752-7021 or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification.

Note: Unless member's health plan has elected not to require, gene and cellular therapies must be administered at an Aetna Institutes® Gene Based, Cellular and Other Innovative Therapy (GCIT®) Network. For Zevaskyn, see Aetna Institutes® GCIT Designated Networks. 

1. Exclusions 

   Aetna considers members with evidence of immune response to C7 by indirect immunofluorescence (IIF) as an exclusion and not eligible for Zevaskyn. 

2. Prescriber Specialties

   This medication must be prescribed by or in consultation with a dermatologist or wound care specialist.

3. Criteria for Initial Approval

   Aetna considers a one dose total of prademagene zamikeracel (Zevaskyn) medically necessary for the treatment of wounds in members with recessive dystrophic epidermolysis bullosa (RDEB) when all of the following criteria are met:

   1. Member is 6 years of age or older; and
   2. Member has clinical manifestations of disease (e.g., extensive skin blistering, skin erosions, scarring); and
   3. Member has genetic test results confirming biallelic pathogenic mutations in the COL7A1 gene; and
   4. Member has positive expression of the non-collagenous region 1 of the type 7 collagen protein (NC1+) in the skin; and
   5. Member has at least one stage 2 chronic wound that will be treated (open for 6 months or more); and
   6. Member does not have a history of squamous cell carcinoma in the affected wound(s) that will receive treatment; and
   7. Member does not have an active infection; and
   8. The requested medication will not be administered to wound(s) that are currently healed; and
   9. Member will not use beremagene geperpavec-svdt (Vyjuvek) or birch triterpenes (Filsuvez) on wounds that have been previously treated with Zevaskyn; and
   10. The requested medication will not be administered to wound(s) that have been previously treated with Zevaskyn.

   Aetna considers all other indications as experimental, investigational, or unproven.

4. Related Policies

   For birch triterpenes (Filsuvez), see Pharmacy Clinical Policy Bulletin Filsuvez SGM 6321-A.

   See also:

   1. CPB 0244 - Skin and Soft Tissue Substitutes
   2. CPB 0334 - Negative Pressure Wound Therapy
   3. CPB 0372 - Wound Imaging and Noninvasive Wound Therapy
   4. CPB 0526 - Surgical Devices, Dressings, and Wound Care Supplies
   5. CPB 1033 - Beremagene Geperpavec-svdt (Vyjuvek)
   6. CPB 1054 - Wound Care: Home or Outpatient Setting
   7. CPB 1087 - Anacaulase-bcdb (NexoBrid).

Dosage and Administration

Zevaskyn is available as single-dose autologous cellular sheets intended for topical use in treating wounds in both adult and pediatric persons with recessive dystrophic epidermolysis bullosa (RDEB). Each sheet measures 41.25 cm² (5.5 cm x 7.5 cm) and consists of the individual's own viable, gene-modified cells that contain functional copies of the COL7A1 gene, which express collagen 7 (C7) protein. Up to 12 C7-expressing cellular sheets are supplied for each surgical session (supplied as up to 3 containers containing up to 4 sheets).

The recommended dose of Zevaskyn is based on the surface area of the wound(s). One sheet covers an area of 41.25 cm². Up to 12 sheets may be manufactured from the person's biopsies and supplied for
potential use.

Zevaskyn is to be prepared by the manufacturer in an appropriate healthcare setting for surgical application by a qualified healthcare provider.

Sheets are topically applied in a single surgical session.

Source: Abeona Therapeutics, 2025b

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
15040	Harvest of skin for tissue cultured skin autograft, 100 sq cm or less
15150 - 15157	Tissue cultured skin autograft, trunk, arms, legs; first 25 sq cm or less
15271 – 15278	Application of skin substitute graft
HCPCS codes covered if selection criteria are met:
J3389	Topical administration, prademagene zamikeracel, per treatment
Other HCPCS codes related to the CPB:
J3401	Beremagene geperpavec-svdt for topical administration, containing nominal 5 x 10^9 pfu/ml vector genomes, per 0.1 ml
ICD-10 codes covered if selection criteria are met:
Q81.2	Epidermolysis bullosa dystrophica [recessive]

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Background

U.S. Food and Drug Administration (FDA)-Approved Indications 

• Zevaskyn is indicated for the treatment of wounds in adult and pediatric patients with recessive dystrophic epidermolysis bullosa (RDEB).

Prademagene zamikeracel, branded as Zevaskyn (Abeona Therapeutics, Inc), is an autologous, genetically modified cellular therapy indicated for the treatment of wounds in patients with recessive dystrophic epidermolysis bullosa (RDEB) resulting from biallelic COL7A1 mutations. Zevaskyn is manufactured by harvesting a patient's keratinocytes via skin biopsy, which are then transduced ex vivo using a replication-deficient gamma-retroviral vector (RVV) encoding the full-length human COL7A1 cDNA. The corrected cells are expanded and fabricated into sterile, single-use epidermal sheets approximately 5.5 x 7.5 cm in size. These cellular sheets are surgically applied under sterile conditions to appropriately cleansed and debrided wounds, where the gene-modified keratinocytes express type VII collagen, facilitating the reconstruction of anchoring fibrils at the dermal-epidermal junction and promoting structural stability and wound healing at the site of application. 

Labeled warnings and precautions include: hypersensitivity reaction to vancomycin, amikacin, or product excipients, which may occur with Zevaskyn application; retroviral vector (RVV)-mediated insertional oncogenesis, which may potentially occur after treatment with Zevaskyn; and transmission of infectious agents, which may occur because Zevaskyn is manufactured using human- and bovine-derived reagents. 

The most common adverse reactions (incidence 5% or more) were procedural pain and pruritus.

There are no available data with use in pregnant women, and no animal reproductive and developmental toxicity studies have been conducted with Zevaskyn. Women of childbearing potential should be advised to use an effective method of contraception.

There is no information regarding the presence of Zevaskyn in human milk, its effect on the breastfed infant, or its effects on milk production. Animal lactation studies have not been conducted with Zevaskyn.

No studies were performed to evaluate the effect of Zevaskyn on fertility.

The safety and effectiveness of Zevaskyn have not been studied in geriatric patients 65 years of age or older.

Recessive Dystrophic Epidermolysis Bullosa (RDEB)

Recessive dystrophic epidermolysis bullosa (RDEB), a subtype of epidermolysis bullosa (EB), is a rare, severe genetic disorder characterized by extremely fragile skin and mucous membranes that easily blister and tear with minimal trauma. It is caused by biallelic (autosomal recessive) mutations in the COL7A1 gene, which encodes type VII collagen, the principal component of anchoring fibrils that secure the epidermis to the dermis. Loss or dysfunction of type VII collagen leads to extreme skin and mucosal fragility, resulting in blistering and erosions from minimal trauma. Healing occurs with significant scarring, fibrosis, and formation of chronic wounds, which can progress to severe deformities such as mitten hand and foot contractures, esophageal strictures, and fusion of oral tissues. Systemic complications include chronic inflammation, anemia, malnutrition, and a markedly increased risk of aggressive cutaneous squamous cell carcinoma, which is the leading cause of death in this population.

Clinical manifestations are typically evident at birth and may involve the entire skin surface and mucous membranes, including the oral cavity, esophagus, and eyes. The disease course is characterized by cycles of blistering, poor wound healing, and progressive fibrosis. The severity of the phenotype can vary, but the severe RDEB form (formerly known as generalized severe, Hallopeau-Siemens RDEB) is the most debilitating.

The diagnosis of dystrophic epidermolysis bullosa (DEB) is established in a proband with characteristic clinical findings and biallelic COL7A1 pathogenic variants for RDEB. Management has been primarily supportive, focusing on wound care, infection prevention, pain control, nutritional support, and surveillance for malignancy. Recently, therapies such as birch triterpenes (Filsuvez, Lichtenheldt GmbH) and beremagene geperpavec (Vyjuvek;  Krystal Biotech, Inc.) have been approved by the FDA for treatment of wounds associated with DEB. Filsuvez is a topical gel derived from birch bark applied to wounds during dressing changes; whereas Vyjuvek is a gene therapy which uses a modified herpes simplex virus (HSV) type 1 vector to non-invasively deliver a gene (COL7A1) to the skin cells, but it does not involve introducing cells into the patient. It is designed to treat wounds in patients with DEB by providing the skin cells with the template to produce the necessary collagen VII protein. It is topically applied as drops once-weekly to a limited number of wounds. 

In April 2025, the FDA approved the first cell-based gene therapy for the treatment of wounds in adult and pediatric patients with RDEB. FDA-approval is based on results from the pivotal Phase III VIITAL trial (NCT04227106) showing Zevaskyn resulted in significant wound healing and pain reduction after a single treatment with a favorable safety profile.

The VIITAL trial is a multicenter, randomized, intrapatient-controlled study that compared the application of Zevaskyn to the standard of care treatment in patients with wounds associated with RDEB. Trial inclusion criteria required participants to have a clinical diagnosis of RDEB, be age 6 years or older, have positive expression of the non-collagenous region 1 of the type 7 collagen protein (NC1+) in the skin, have two confirmed RDEB C7 mutations with recessive inheritance patterns (or confirmation that parents don't have any evidence of dominant disease), and have at least 40 cm2 areas of chronically wounded area on the trunk and/or extremities suitable for application (open erosions). Participants were excluded if they had evidence of immune response to C7 by indirect immunofluorescence (IIF), evidence of systemic infection, and current evidence or a history of squamous cell carcinoma (SCC) in the area that will undergo application. A total of 86 wounds (n=43 Zevaskyn-treated; n=43 control wounds) in 11 patients were treated with Zevaskyn or standard of care. The trial met both co-primary endpoints at 6 months post-treatment: 81% of Zevaskyn-treated wounds achieved 50% or more healing compared to 16% in standard-of-care control wounds (P<0.0001), and wounds treated with Zevaskyn showed significantly greater pain reduction on the Wong-Baker FACES scale. The most common adverse events were observed in fewer than five percent of patients and included procedural pain and itch.

In the Phase 1/2a study of Zevaskyn (NCT01263379), a single center, open label study in 38 chronic wounds across 7 patients showed that a single surgical application of Zevaskyn was associated with long-term improvement at treated sites over a median follow-up of 6.9 years (range 4 to 8 years) (Abeona Therapeutics, 2025a).

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References