The FDA approved Beremagene Geperpavec (B-VEC), also known by its trade name Vyjuvke, on May 19, 2023, for the treatment of dystrophic maculopapularity in patients aged 6 months and older with epidermolysis bullosa (DEB), caused by a COL7A1 gene mutation. B-VEC, developed by Krystal Biotech, Inc., is a topical gene therapy based on herpes simplex virus type 1 (HSV-1). It is noteworthy for being the first topical gene therapy approved by the FDA, as well as the first repeatable gene therapy and the first gene therapy specifically for treating dystrophic herpetic epidermolysis bullosa (DEB).
Dystrophic Epidermolysis Bullosa (DEB) is an uncommon genetic skin disorder resulting from mutations in the COL7A1 gene, responsible for encoding type VII collagen (C7). This genetic condition makes patients highly susceptible to the development of extensive and hemorrhagic blisters on their skin. These individuals are commonly referred to as “butterfly babies” due to the delicate nature of their skin, which can be easily damaged with the slightest touch, resembling the fragility of a butterfly. DEB stands out as one of the most excruciating diseases worldwide, with patients being vulnerable to infections, skin cancer, and even fatal outcomes.
Beremagene Geperpavec (B-VEC) is an investigational topical gene therapy based on HSV-1 designed to treat dystrophic maculopapular epidermolysis bullosa by restoring collagen type VII (C7) expression through the delivery of the COL7A1 gene. The B-VEC therapy innovatively uses a gel-based topical delivery method so that it is administered in the form of an application to the patient’s skin wound, followed by bandage protection. Because this gene therapy is administered topically, it requires long-term repeat dosing and cannot provide a one-time cure like previous recombinant adeno-associated virus (AAV)-based gene therapies. Krystal Biotech says the therapy costs $24,250 per vial, and patients use an average of 26 vials per year, or up to $630,000 per year for treatment, which after a mandatory government discount still costs $485,000.
On December 15, 2022, a team of researchers from Stanford University School of Medicine published a research paper in the New England Journal of Medicine (NEJM) titled Trial of Beremagene Geperpavec (B-VEC) for Dystrophic Epidermolysis Bullosa. The results of this phase 3 clinical trial showed that the topical administration of B-VEC therapy significantly promoted complete wound healing at 3 and 6 months in patients with dystrophic epidermolysis bullosa.
This is a phase 3, randomized, double-blind, placebo-controlled trial of 31 patients aged 6 months or older with genetically sequenced-confirmed dystrophic epidermolysis bullosa due to a mutation in the COL7A1 gene. The study team selected a pair of skin wounds for each patient, matched for wound size, area, and appearance. Each patient’s wound pair was then randomly assigned to receive either B-VEC or placebo therapy for a period of 26 weeks.
The primary endpoint of this phase 3 clinical trial was the complete healing of treated wounds compared to untreated wounds after 6 months of treatment. Secondary endpoints included complete wound healing at 3 months and a change in pain severity at reapplication (bandage replacement).
The trial results revealed that after 6 months, 67% of wounds treated with B-VEC exhibited complete healing, whereas only 22% of wounds treated with placebo achieved the same outcome. Similarly, at the 3-month mark, 71% of the wounds treated with B-VEC were completely healed, in contrast to the 20% healing rate observed in the placebo group.
Overall, the results of this phase 3 clinical trial showed that topically administered B-VEC therapy significantly promoted complete wound healing at 3 and 6 months in patients with dystrophic maculopapular epidermolysis bullosa. Pruritus and mild systemic side effects were observed in patients during treatment.
Founded in 2015, Krystal Biotech is focused on developing gene therapies for severe rare diseases caused by deletions or mutations in a single gene. In addition to B-VEC therapies, the company has several clinical-stage gene therapies for autosomal recessive ichthyosis with defects in the TGM1 gene, cystic fibrosis, and anti-aging skin treatments that rely on type 3 collagen.