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Beremagene Geperpavec (Vyjuvek™)
08.02.10

Policy

MEDICALLY NECESSARY

INITIATION THERAPY

Beremagene Geperpavec (Vyjuvek™) is considered medically necessary and, therefore, covered  in individuals six months and older for the tretatment of wounds in individuals with dystrophic epidermolysis bullosa (DEB) when ALL of the following criteria are met:

  • Diagnosis of dystrophic epidermolysis bullosa (DEB); and 
  • Submission of medical records (e.g., chart notes, laboratory values) confirming a pathogenic variation in the collagen type VII alpha 1 chain (COL7A1) gene; and 
  • Individual has at least one recurrent or chronic open wound that meets all of the following criteria: 
    • Adequate granulation tissue 
    • Excellent vascularization 
    • No evidence of active wound infection 
    • No evidence or history of squamous cell carcinoma 
  • Individual did not have a skin graft in the past three months
  • 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; and  
  • Initial authorization will be issued for no more than 6 months and no more than 26 doses

CONTINUATION THERAPY

Continued therapy with Beremagene Geperpavec (Vyjuvek™) is considered medically necessary and, therefore, covered when ALL of the following criteria are met whi:

  • Individual has previously been treated with Vyjuvek therapy 
  • Individual 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 following criteria: 
    • Adequate granulation tissue 
    • Excellent vascularization
    • No evidence of active wound infection 
    • No evidence or history of squamous cell carcinoma 
  • Individual did not have a skin graft in the past three months
  • 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; and 
  • Reauthorization will be issued for no more than 6 months and no more than 26 doses​

​EXPERIMENTAL/INVESTIGATIONAL 

All other uses for Beremagene Geperpavec (Vyjuvek™) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.


Guidelines

U.S. FOOD AND DRUG ADMINISTRATION (FDA)

On May 19, 2023, the U.S. Food and Drug Administration approved Vyjuvek, a herpes-simplex virus type 1 (HSV-1) vector-based gene therapy, for the treatment of wounds in patients 6 months of age and older with dystrophic epidermolysis bullosa (DEB) with mutation(s) in the collagen type VII alpha 1 chain (COL7A1) gene. 

DOSAGE, FREQUENCY, AND ADMINISTRATION

See Package Insert: https://www.fda.gov/media/168350/download?attachment

  • The recommended dose of Vyjuvek is based on age and is applied topically to wound(s) once a week.
  • Only a healthcare professional should apply Vyjuvek gel either at a healthcare professional setting (e.g., clinic) or the home setting.

-- A warning and precaution for Vyjuvek is accidental exposure to Vyjuvek. 

-- The most common adverse reactions (> 5%) with Vyjuvek use were itching, chills, redness, rash, cough, and runny nose. 

-- It may not be possible to apply Vyjuvek gel to all the wounds at each treatment visit.

-- Vyjuvek should be applied to wounds until they are closed before selecting new wound(s) to treat. 

-- Weekly treatment to previously treated wounds if they re-open should be prioritized.

-- Vyjuvek is a biological suspension, mixed into excipient gel. 
-- Vyjuvek biological suspension is supplied as a 1.0 mL extractable volume in a single dose vial at a nominal concentration of 5×109 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.

Description

DYSTROPHIC EPIDERMOLYSIS BULLOSA (DEB)

Eepidermolysis Bullosa (EB) is an ultra-rare genetic disorder that causes abnormalities in the cohesion of layers of the skin, resulting in blisters, erosions, nonhealing ulceration, and scars in response to even mild skin trauma. Complications of EB can include infection, squamous cell carcinoma, constipation, hair loss, and anemia among others. 

DEB is one of four types of EB and is caused by mutations in the COL7A1 gene which codes for Type VII collagen that helps bind the dermis to the epidermis. The extent of skin fragility in DEB varies depending on whether the causative mutation predisposes the patient to mild or severe disease and whether the Type VII collagen is completely absent or reduced. The prevalence of DEB is about 3.26 per million population with an incidence of 6.65 per million live births. 

DEB is categorized as recessive or dominant(D), with recessive(R) being the more severe form. Symptoms can vary widely among affected people. 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.Individuals with DDEB generally survive to adulthood with few complications; however, those with RDEB may only survive to their third or fourth decade if managed appropriately, with the major causes of death being metastatic squamous cell carcinoma and renal failure. There are no FDA approved treatments and there is no cure for any type of EB. Disease management is primarily supportive and multidisciplinary, involving wound care, pain control, infection control, nutritional support, and treatment of complications.

VYJUVEK

 

Vyjuvek is a topical gene therapy that uses a herpes simplex virus (HSV-1) to introduce a normal copy of the COL7A1 gene to indivuals' skin cells. Once Vyjuvek enters the nucleus of transduced cells, the vector genome is deposited episomally and as a result, COL7A1 transcripts are generated, allowing the cell to produce and secrete functional CO7A1 protein necessary for the formation of anchoring fibrils that bind the dermis and epidermis together, and blistered skin to be replaced with healthy skin. The COL7A1 gene does not incorporate itself into individuals' chromosomes; therefore, patients must be treated with Vyjuvek repeatedly in order to continue producing healthy skin.


PEER-REVIEWED LITERATURE 

The efficacy of Vyjuvek gel in subjects one year of age and older with dystrophic epidermolysis bullosa (DEB) with mutation(s) in the COL7A1 gene was evaluated in one randomized, double-blind, intra-subject placebo-controlled trial. All study subjects had clinical manifestations consistent with DEB and genetically confirmed mutation(s) in the COL7A1 gene. Two comparable wounds in each subject were selected and randomized to receive either topical application of Vyjuvek gel or the placebo (excipient gel) weekly for 26 weeks. The study enrolled 31 subjects (20 males and 11 females), including 30 subjects with autosomal recessive DEB and one subject with autosomal dominant DEB. The size of the Vyjuvek gel-treated wounds ranged from 2 to 57 cm2, with 74% of wounds < 20 cm2 and 19% from 20 to < 40 cm2. The size of the placebo gel-treated wounds ranged from 2 to 52 cm2, with 71% of wounds < 20 cm2 and 26% from 20 to < 40 cm2. The mean age of the subjects was 17 years (1 year to 44 years), including 61% pediatric subjects (n = 19, age from 1 year to < 17 years). Sixty-four percent of subjects were White; 19% were Asian, and the remainder were American Indian or Alaska Native. Efficacy was established on the basis of improved wound healing defined as the difference in the proportion of complete (100%) wound closure at 24 Weeks confirmed at two consecutive study visits 2 weeks apart, assessed at Weeks 22 and 24 or at Weeks 24 and 26, between the Vyjuvek gel-treated and the placebo gel-treated wounds. Efficacy was supported by the difference in the proportion of complete wound closure assessed at Weeks 8 and 10 or at Weeks 10 and 12 between the Vyjuvek gel-treated and the placebo geltreated wounds. Complete (100%) wound closure was defined as durable wound closure evaluated at two consecutive visits two weeks apart. 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 (difference, 46 percentage points; 95% confidence interval [CI], 24 to 68; 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 (difference, 51 percentage points; 95% CI, 29 to 73; 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.


A total of 18 individuals (58%) had at least one adverse event. The majority of adverse events were mild or moderate in severity, as assessed by the investigators. Five serious adverse events occurred in 3 individuals: 1 individual was hospitalized three times, once for diarrhea and twice for severe anemia; 1 individual was hospitalized for treatment of cellulitis; and 1 individual was hospitalized for a positive blood culture related to a hemodialysis catheter. None of the serious adverse events were considered to be related to B-VEC or placebo by the investigators. One adverse event, mild erythema, was considered to be related to BVEC. No adverse events led to discontinuation of B-VEC or placebo. The most common adverse events were pruritus, chills, and squamous-cell carcinoma of the skin, each of which occurred in 3 individuals (10%). All three cases of squamous-cell carcinoma occurred at wound sites that had not been exposed to B-VEC or placebo.


To determine potential immunogenicity, levels of antibodies against HSV-1 and C7 before and after treatment were assessed. Because of the difficulty of venipuncture in these individuals, 22 of 31 individuals (71%) had baseline serum samples. Among the individuals with baseline samples, 14 of 22 individuals (64%) had antibodies against HSV-1, a finding consistent with the prevalence of seropositivity in the U.S. population, and 1 of 22 individuals (5%) had antibodies against C7. Among the individuals with baseline samples, 19 had samples at both baseline and week 26, including the individual who had antibodies against C7. By week 26, seroconversion had occurred in 6 of 8 individuals (75%) with no antibodies against HSV-1 at baseline and in 13 of 18 (72%) with no antibodies against C7 at baseline. No clinically significant immunologic reactions were reported. Treatment response to B-VEC was not associated with baseline HSV-1 serostatus or C7 seroconversion.​


SUMMARY

Dystrophic epidermolysis bullosa (DEB) is an ultra-rare genetic connective tissue disorder caused by mutations in the collagen type VII alpha 1 chain (COL7A1) gene. The COL7A1 gene codes for type VII collagen (C7), a major component of structures in the skin called anchoring fibrils found in the epidermal basement membrane located between the epidermis (top layer of skin) and dermis (underlying layer). Mutations in the COL7A1 gene disrupt adhesion of the epidermis to the dermis. Individuals with EB completely lack or are deficient in COL7A1, resulting in skin fragility and multiple recurring wounds that are difficult to manage. Over time, repeated blistering and fibrosis can lead to squamous-cell carcinoma, life-threating infections, and limb deformities. DEB may be inherited as a dominant or recessive trait; generally, RDEB is more severe than dominant disease (DDEB); however, there is considerable phenotypic overlap between types. DEB affects approximately 9,000 people globally, including approximately 3,000 people in the U.S. and approximately 3,000 in Europe. The current standard of care is supportive treatment with wound care and prevention of infection. 

Diagnosis confirmation through genetic testing, immunofluorescence mapping (IFM) and/or transmission of electron microscopy (TEM) can be done to determine a precise subclassification. Currently, there have not been any definitive treatments and symptomatic care is the mainstay of disease management. The prevention of new blisters along with wound care have been the primary treatment for this disease. ​

Vyjuvek is a herpes-simplex virus type 1 vector-based gene therapy that delivers normal copies of the COL7A1 gene to the wounds. Vyjuvek has also been modified to eliminate its ability to replicate in normal cells. Vyjuvek is the first FDA approved therapy for DEB. The efficacy of Vyjuvek was established in a randomized, double-blind, intra-subject placebocontrolled study in 31 patients with DEB. Two comparable wounds in each subject were selected and randomized to receive either topical application of Vyjuvek gel or the placebo (excipient gel) weekly for 26 weeks.  Efficacy was supported by the difference in the proportion of complete wound closure assessed at Weeks 8 and 10 or at Weeks 10 and 12 between the VYJUVEK gel-treated and the placebo gel-treated wounds. Complete (100%) wound closure was defined as durable wound closure evaluated at two consecutive visits two weeks apart. Efficacy was further established on the basis of improved wound healing defined as the difference in the proportion of complete (100%) wound closure at 24 weeks confirmed at two consecutive study visits 2 weeks apart, assessed at weeks 22 and 24 or at weeks 24 and 26, between the Vyjuvek gel-treated and the placebo gel-treated wounds.​ Complete wound closure at 24 weeks was achieved for 65% of wounds treated with Vyjuvek vs. 26% with placebo (treatment difference 39%, 95% CI: 14, 63; p = 0.012).​

Summary of the efficacy results for VYJUVEK gel (Intention-to-treat (ITT) Population) 

Wound Closure Assessment Timepoints Complete
Wound Closure, n (%) VYJUVEK gel (N=31)
Complete Wound Closure, n (%) Placebo gel (N=31)  Treatment Difference (95% CI)   p value 

Weeks 22 & 24 or Weeks 24 & 26                                         20 (65)                                                                               8 (26)                                                                         39% (14, 63)      0.012
Weeks 8 & 10 or Weeks 10 & 12                                           21 (68)                                                                               7 (23)                                                                         45% (22, 69)      0.003


References

A Phase III Efficacy and Safety Study of Beremagene Geperpavec (B-VEC, Previously "KB103") for the Treatment of Dystrophic Epidermolysis Bullosa (DEB). ClinicalTrials.gov identifier: NCT04491604. Updated February 17, 2023. Accessed June 30, 2023. https://classic.clinicaltrials.gov/ct2/show/study/NCT04491604.


Clinical Study to Compare the Efficacy and Safety of Beremagene Geperpavec (B-VEC) Topical Gel with That of Placebo for the Treatment of Dystrophic Epidermolysis Bullosa (DEB). ClinicalTrials.gov identifier: NCT04491604. Updated August 3, 2022. https://www.clinicaltrials.gov/ct2/show/NCT04491604.


DailyMed. Package inserts. U.S. National Library of Medicine, National Institutes of Health website. http://dailymed.nlm.nih.gov/dailymed/about.cfm.


DrugPoints® System [electronic version]. Truven Health Analytics, Greenwood Village, CO. Updated periodically.


Guide SV, Gonzalez ME, Bağcı IS, Agostini B, Chen H, Feeney G, Steimer M, Kapadia B, Sridhar K, Quesada Sanchez L, Gonzalez F, Van Ligten M, Parry TJ, Chitra S, Kammerman LA, Krishnan S, Marinkovich MP. Trial of Beremagene Geperpavec (B-VEC) for Dystrophic Epidermolysis Bullosa. N Engl J Med. 2022 Dec 15;387(24):2211-2219. doi: 10.1056/NEJMoa2206663. PMID: 36516090.


Lexi-Comp ONLINE™ with AHFS™, Hudson, Ohio: Lexi-Comp, Inc. Updated periodically.


Open Label Treatment of Beremagene Geperpavec (B-VEC). ClinicalTrials.gov identifier: NCT04917874. Updated April 2023. Accessed June 30, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04917874.


Vyjuvek [package insert]. Pittsburg, PA: Krystal Biotech, Inc.; May 2023.


Coding

CPT Procedure Code Number(s)
N/A

ICD - 10 Procedure Code Number(s)
N/A

ICD - 10 Diagnosis Code Number(s)
Q81.2 Epidermolysis bullosa dystrophica

HCPCS Level II Code Number(s)
THE FOLLOWING CODES REPRESENT BEREMAGENE GEPERPAVEC (VYJUVEK™) 

C9399 Unclassified drugs or biologicals

J3590 Unclassified biologics​

Revenue Code Number(s)
N/A


Coding and Billing Requirements


Policy History

9/11/2023
9/11/2023
08.02.10
Medical Policy Bulletin
Commercial
No