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

Beremagene geperpavec-svdt (B-VEC) is available as Vyjuvek (Krystal Biotech, Inc.). Vyjuvek is a topical gene therapy gel that works by delivering functional human

gene copies directly into open wounds via a modified herpes simplex virus type 1 (HSV-1). Vyjuvek 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

gene, which results in reduced or absent levels of biologically active COL7.

Vyjuvek is a biological suspension, mixed into excipient gel, for topical application by a healthcare provider. There are no labeled contraindications. Warnings and precaution include avoiding direct contact with treated wounds and dressings of treated wounds for approximately 24 hours following application. The most common adverse drug reactions (incidence greater than 5%) were 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

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

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

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.

: 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),

For Medicare Part B plans, call (866) 503-0857, or fax (844) 268-7263.

Prescriber Specialties

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

Criteria for Initial Approval

Aetna considers beremagene geperpavec-svdt (Vyjuvek) medically necessary for treatment of wounds in members with dystrophic epidermolysis bullosa (DEB) when

of the following criteria are met:

Aetna considers all other indications as experimental and investigational.