Beremagene Geperpavec-svdt (Vyjuvek)

Number: 1033

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 beremagene geperpavec-svdt (Vyjuvek) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Vyjuvek has been identified as an Aetna Gene-based, Cellular & Other Innovative Therapies (GCIT®) product that receives dedicated review by the Aetna GCIT team for Commercial lines of business.

Note: Requires Precertification: 

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

1. Prescriber Specialties

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

2. Criteria for Initial Approval

   Aetna considers beremagene geperpavec-svdt (Vyjuvek) medically necessary for treatment of wounds in members with dystrophic epidermolysis bullosa (DEB) when all of the following criteria are met:

   1. Member has clinical manifestations of disease (e.g., extensive skin blistering, skin erosions, scarring); and
   2. Member has genetic test results confirming a pathogenic or likely pathogenic variant in the COL7A1 gene; and
   3. Member has one or more open wounds that will be treated (i.e., target wounds); and
   4. Target wound(s) meet all of the following:
       
      1. Wound is clear in appearance and does not appear to be infected; and
      2. Wound has adequate granulation tissue and vascularization; and
      3. Member does not have a history of squamous cell carcinoma in the affected wound(s) that will receive treatment; and
   5. Member has not received a skin graft in the past three months; and
   6. Member will not receive prademagene zamikeracel (Zevaskyn) or use birch triterpenes (Filsuvez) on wounds that have previously been treated with Vyjuvek; and
   7. Vyjuvek will be administered once weekly to the affected wound(s) by a healthcare professional, member, or caregiver either at a healthcare professional setting (e.g., clinic) or a home setting; and
   8. Vyjuvek will not be administered to wound(s) that are currently healed.

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

3. Related Policies 

   • CPB 0244 - Skin and Soft Tissue Substitutes

Dosage and Administration

Vyjuvek is a biological suspension mixed with excipient gel for topical application.

The Vyjuvek gel prepared at the pharmacy, should be applied by a healthcare professional (HCP), patient, or caregiver either at a healthcare professional setting (e.g., clinic) or at a home setting.

Vyjuvek is supplied as a 1 mL extractable volume in a single-use vial at a nominal concentration of 5×10⁹ plaque forming unit per milliliter (PFU/mL). The excipient gel is supplied as a 1.5 mL fill volume in a separate single-use vial. Vyjuvek biological suspension (1 mL) is mixed into the excipient gel vial prior to administration as Vyjuvek gel.

The recommended dose is based on age (see Table below) and is applied topically to wound(s) once a week.

Table: Maximum Weekly Dose by Age

Age Range	Maximum Weekly Dose (PFU)	Maximum Weekly Volume (mL)Footnote1*
less than 3 years old	2 x 109	1
3 years of age and older	4 x 109	2

Footnote1*Maximum weekly volume after mixing Vyjuvek biological suspension with excipient gel.

Per the label:

• It may not be possible to apply Vyjuvek gel to all the wounds at each treatment visit.
• Apply Vyjuvek gel to wounds until they are closed before selecting new wound(s) to treat.
• Prioritize weekly treatment to previously treated wounds if they re-open. 
• If a dose is missed, apply Vyjuvek gel as soon as possible and resume weekly dosing thereafter.

Source: Krystal Biotech, 2025b

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
15002 – 15005	Surgical preparation [Skin graft]
15011 – 15018	Skin Cell Suspension Autograft
15040 – 15261	Autografts/tissue cultured autograft
15271 – 15278	Skin substitute grafts
HCPCS codes covered if selection criteria are met:
J3401	Beremagene geperpavec-svdt for topical administration, containing nominal 5 x 10^9 pfu/ml vector genomes, per 0.1 ml
Other HCPCS codes related to the CPB:
Birch triterpenes (Filsuvez) - no specific code
J3389	Topical administration, prademagene zamikeracel, per treatment
ICD-10 codes covered if selection criteria are met:
Numerous options	Open wounds
Q81.2	Epidermolysis bullosa dystrophica
ICD-10 codes not covered for indications listed in the CPB:
Z85.828	Personal history of other malignant neoplasm of skin [squamous cell carcinoma]

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Background

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

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

Beremagene geperpavec-svdt (B-VEC), a herpes-simplex virus type 1 (HSV-1) vector-based gene therapy,  is marketed as Vyjuvek (Krystal Biotech, Inc.). Vyjuvek is a topical gene therapy gel that works by delivering functional human COL7A1 gene copies directly into open wounds via a modified HSV-1. This therapy is aimed to produce a type of collagen that will promote wound healing in patients with dystrophic epidermolysis bullosa (DEB) who have a mutation in the collagen type VII alpha 1 chain (COL7A1) gene. These mutations lead to reduced or absent levels of biologically active type VII collagen, which is crucial for skin integrity.

Vyjuvek is a biological suspension mixed into an excipient gel for topical application, which should be applied by a healthcare professional, patient, or caregiver in either a healthcare professional setting (e.g., clinical) or home setting.

While there are no contraindications, pregnant individuals are advised against preparing or applying the gel and should avoid direct contact with treated wounds or their dressings. Additionally, labeled warnings highlight the risk of accidental exposure, necessitating avoidance of contact with treated areas until the next dressing change, and advising cleaning of the area if exposure occurs. Common adverse reactions occurring in more than 5% of users include itching, chills, redness, rash, cough, and runny nose.

Dystrophic Epidermolysis Bullosa 

Dystrophic epidermolysis bullosa (DEB) is a rare, inherited disorder that is characterized by blistering of the skin and mucosal membranes that heal with scarring. DEB is caused by mutations in the COL7A1 gene, encoding the alpha-1 chain of type VII collagen (COL7) which is an "essential protein that helps strengthen and stabilize the outer and middle layers of the skin. When COL7A1 is deficient, skin layers can separate, causing painful and debilitating blisters and wounds" (FDA, 2023). 

DEB may be inherited in an autosomal dominant or autosomal recessive manner depending on the subtype, and depending on the inheritance pattern, DEB is divided into two major types: recessive dystrophic epidermolysis bullosa (RDEB) and dominant dystrophic epidermolysis bullosa (DDEB). "Individuals with DDEB typically have mild cases with blistering primarily affecting the hands, feet, knees, and elbows. RDEB cases can be painful and debilitating, often involving widespread blistering that can lead to vision loss, disfigurement, and other serious medical complications, which could be fatal" (FDA, 2023).

According to the National Institutes of Health / Genetic and Rare Diseases (GARD) Information Center, fewer than 5,000 people in the United States have DEB. Symptoms of the disease can vary and may start to appear in infancy. Treatment for DEB has included supportive care, such as prevention of blistering, daily wound care, bandaging, and pain management as needed.

In May 2023, the U.S. FDA approved the first topical gene therapy, Vyjuvek (Krystal Biotech, Inc.), for the treatment of wounds in patients with DEB who have mutation(s) in the COL7A1 gene. FDA approval is based on positive outcomes from the GEM-3 clinical trial (NCT04491604), which was a randomized, double-blind, intra-patient placebo-controlled, phase 3 study designed to evaluate the efficacy and safety of beremagene geperpavec (B-VEC), known as Vyjuvek, for the treatment of DEB. 

Guide et al. (2022) conducted the GEM-3 trial to evaluate the safety and efficacy of B-VEC in patients 6 months of age or older with genetically confirmed DEB. The age of the patients enrolled in the study ranged from 1 year to 44 years (mean age 17 years). For each patient, two primary DEB wounds were selected, with the wounds matched according to size, region, and appearance. The wounds within each pair were randomly assigned in a 1:1 ratio to receive weekly application of either B-VEC or placebo for 26 weeks. The primary end point was complete wound healing of treated as compared with untreated wounds at 6 months. Secondary end points included complete wound healing at 3 months and the change from baseline to weeks 22, 24, and 26 in pain severity during changes in wound dressing, assessed with the use of a visual analogue scale (scores range from 0 to 10, with higher scores indicating greater pain). The authors state that primary wound pairs were exposed to B-VEC and placebo in 31 patients. The authors found that at 6 months, complete wound healing occurred in 67% of the wounds exposed to B-VEC as compared with 22% of those exposed to placebo (p= 0.002). Complete wound healing at 3 months occurred in 71% of the wounds exposed to B-VEC as compared with 20% of those exposed to placebo (p<0.001). The mean change from baseline to week 22 in pain severity during wound-dressing changes was -0.88 with B-VEC and -0.71 with placebo (adjusted least-squares mean difference, -0.61; 95% CI, -1.10 to -0.13); similar mean changes were observed at weeks 24 and 26. Adverse events with B-VEC and placebo included pruritus and chills. The authors concluded that complete wound healing at 3 and 6 months in patients with DEB was more likely with topical administration of B-VEC than with placebo; however, longer and larger trials are warranted to determine the durability and side effects of B-VEC for this disease. Patients returned to the clinical site 30 days following the last dosing visit (Week 26) for safety evaluation by the investigator and subsequently had the option to roll into the Open Label Extension (OLE) Study (NCT04917874).

In addition, in a different clinical study, two young patients with RDEB (6 and 7 months of age, respectively) received topical Vyjuvek weekly without any new safety findings (FDA, 2023).

Vyjuvek gel is not to be administered to wound(s) that are currently healed.

In September 2025, the FDA approved a label update for Vyjuvek that expands the eligible patient population to include patients with DEB from birth. This update also permits DEB patients, or their caregivers, to apply Vyjuvek at home. Additionally, wound dressings can now be removed as part of the next dressing change instead of waiting 24 hours. FDA approval is based on real-world data collected since the launch of Vyjuvek in the United States, as well as results from a published open-label extension study (ClinicalTrials.gov ID NCT04917874) by Marinkovich et al. (2025). The Vyjuvek label states that the use in pediatric patients (0 to 16 years of age) was supported by evidence from adequate and well-controlled study which included 19 pediatric patients 1 year of age and older.

In an open-label extension study, Marinkovich et al. (2025) aimed to evaluate the safety and tolerability of B-VEC beyond 6 months in patients with dystrophic epidermolysis bullosa (DEB). The study included 47 subjects, comprising 24 rollover participants from a phase III trial and 23 treatment-naïve individuals, who received weekly applications of B-VEC to target wound areas for up to 112 weeks (median 81 weeks). Safety was assessed through the monitoring of adverse events, while treatment satisfaction and quality of life were evaluated using patient-reported outcomes as exploratory measures of efficacy. Results indicated that 35 subjects (74.5%) reported one or more adverse events, primarily mild or moderate in severity, with 14 subjects experiencing 17 serious adverse events and ten experiencing 14 severe adverse events, none of which were considered treatment-related. No adverse events led to treatment or study discontinuation. Patient-reported outcomes reflected high levels of treatment satisfaction, although quality of life results were inconclusive. Among rollover subjects, wounds treated with B-VEC during the phase III trial maintained high closure rates during the open-label extension, ranging from 61.1% to 89.5% from baseline to month 12. Despite the study's open-label design and variable follow-up, the findings suggest that patients receiving extended B-VEC treatment maintained high satisfaction and continued to respond positively, with no new safety signals detected, thereby supporting the ongoing use of B-VEC.

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References