RARE Daily

NEJM Publication Suggests Potential of Reformulated Version of Krystal’s Gene Therapy to treat Eye Disease

February 8, 2024

Rare Daily Staff

Krystal Biotech last year won U.S. Food and Drug Administration approval for Vyjuvek, a groundbreaking topical formulation of its B-VEC gene therapy applied to the skin for the rare connective tissue disorder dystrophic epidermolysis bullosa. Notable about the treatment is that it is the first redosable gene therapy and the first and only treatment for patients with the condition.

Dystrophic epidermolysis bullosa (DEB) affects the skin and mucosal tissues caused by one or more mutations in the COL7A1 gene. The COL7A1 gene is responsible for the production of functional COL7 protein that forms anchoring fibrils necessary to bind the dermis (inner layer of the skin) to the epidermis (outer layer of the skin). The lack of functional anchoring fibrils in DEB patients leads to extremely fragile skin that blisters and tears with minor friction or trauma. DEB patients suffer from open wounds, which leads to skin infections, fibrosis that can cause fusion of fingers and toes, and ultimately an increased risk of developing an aggressive form of squamous cell carcinoma that, in severe cases, can be fatal.

B-VEC is a non-invasive, redosable gene therapy built to deliver two copies of the COL7A1 gene to treat DEB at the molecular level by providing the patient’s cells the template to make normal COL7 protein, thereby addressing the fundamental disease-causing mechanism.

Now, a new publication in the New England Journal of Medicine reports on the first application of B-VEC administered as an eyedrop to treat ocular complications in a patient with DEB under a compassionate use program. More than 25 percent of patients with DEB develop ocular complications such as corneal erosions, abrasions, blistering and scarring that can lead to impaired vision. Currently the treatment of such cases ranges from supportive care and wound management to surgical interventions to remove scar tissue. No corrective therapy is presently available.

In the study, the patient presented with severe cicatrizing conjunctivitis secondary to DEB. Surgical symblepharon lysis of the patient’s right eye with pannus removal was conducted and regular administration of B-VEC as an eyedrop directly to the eye were added to routine post-surgical care, three times weekly for the first two weeks and then once weekly. The application frequency of B-VEC was further decreased to once monthly once the corneal epithelium was healed. The gene therapy was well tolerated and associated with full corneal healing by three months as well as significant visual acuity improvement from hand motion to 20/25 at eight months.

“DEB is a devastating disease and patients with ocular complications have no corrective treatment options leaving them at risk of severe vision loss,” said Alfonso Sabater, associate professor of clinical ophthalmology at the Bascom Palmer Eye Institute at the University of Miami Miller School of Medicine, and investigator. “We are encouraged by the improvements observed in the patient following B-VEC administration as an eyedrop directly to the affected eye and believe this data is supportive of further investigation in DEB patients with ocular complications. If approved, this approach could drastically benefit these patients.”

Suma Krishnan, president of research and development for Krystal Biotech, said the company is working with the FDA to get B-VEC approved for the treatment of DEB patients with lesions in the eye.

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