NEW YORK – The US Food and Drug Administration on Friday approved Krystal Biotech's topical gene therapy Vyjuvek (beremagene geperpavec-svdt) for treating wounds in pediatric and adult patients with dystrophic epidermolysis bullosa due to mutations in the collagen type VII alpha 1 chain (COL7A1) gene.
COL7A1 encodes type VII collagen, a protein necessary for strengthening the outer and middle layers of the skin. Patients with dystrophic epidermolysis bullosa (DEB) have a deficiency of this critical protein and develop painful blisters as a result; patients with the dominant form of the disease have milder symptoms, but those with the recessive form develop wounds that can be disfiguring, cause vision loss, and may be fatal.
Vyjuvek, the first gene therapy for treating DEB-related wounds, uses a genetically modified herpes-simplex virus type 1 vector to deliver a normal version of the COL7A1 gene to patients.
"COL7 molecules arrange themselves into long, thin bundles that form anchoring fibrils that hold the epidermis and dermis together, which is essential for maintaining the integrity of the skin," the FDA said in an announcement about Vyjuvek's approval. The topical treatment, which must be applied weekly by a healthcare professional directly to patients' wounds, is designed to not replicate in normal cells.
"Until now, doctors and nurses had no way to stop blisters and wounds from developing on DEB patient skin, and all we could do was to give them bandages and helplessly watch as new blisters formed," M. Peter Marinkovich, director of the Blistering Disease Clinic at Stanford Health Care and primary investigator of one of the trials that led to Vyjuvek's approval, said in a statement. "Vyjuvek topical gene therapy changes all of this. Vyjuvek both heals patient wounds and prevents skin from re-blistering because it actually corrects the underlying skin defect of DEB."
He added that as a gene therapy that's topically applied, Vyjuvek doesn't require advanced technology or specialized expertise to administer and therefore will be accessible to patients who live far from specialized centers.
The agency approved Vyjuvek based primarily on data from a trial in which 31 DEB patients with two wounds of similar size were randomized to receive weekly administration of the gene therapy or placebo. Patients were between 1 year and 44 years old. In 65 percent of Vyjuvek-treated patients, the wounds completely closed versus 26 percent of the placebo-treated patients.
It was common for patients receiving the gene therapy to experience itching, chills, redness, rash, cough, and runny nose. In another study, two patients, a 6-month-old and 7-month-old, received Vyjuvek and didn't experience any new adverse events. The FDA cautioned patients and caregivers to avoid touching the wounds for 24 hours after applying Vyjuvek and to wash their hands if they come into contact with the wounds during this time, and instructed them on proper cleaning and disposal of bandages.
Krystal Biotech said in a statement that Vyjuvek will be available to US patients in Q3. The Pittsburgh-based firm will launch Krystal Connect, a program through which patients and caregivers can learn about the drug and about financial assistance. The firm plans to seek marketing authorization in Europe in the second half of the year and is working with regulators in Japan to submit the necessary data there.