New Gene Therapy for Skin Wounds Improved Vision in Young Boy

Derick Alison
Derick Alison
7 Min Read

Ophthalmic administration of beremagene geperpavec (B-VEC; Vyjuvek) improved visual acuity in a young patient with cicatrizing conjunctivitis due to dystrophic epidermolysis bullosa, researchers reported.

With treatment with topical B-VEC applied directly to the right eye, visual acuity improved from hand motion (log10 of the minimal angle of resolution [logMAR] 3.00) before surgery to 20/25 (logMAR 0.10) without correction at 8 months post surgery in a 13-year-old boy with recessive dystrophic epidermolysis bullosa, said Arianna Tovar Vetencourt, MD, of the Bascom Palmer Eye Institute at the University of Miami Miller School of Medicine, and colleagues.

There was also no recurrence of symblepharon or corneal scarring for up to 8 months post surgery, they noted in the New England Journal of Medicine.

Furthermore, no signs of ocular herpes simplex virus type 1 (HSV-1)-like disease emerged in the boy, who was deemed legally blind and diagnosed with recessive dystrophic epidermolysis bullosa at age 7.

“Our data support further investigation of B-VEC in the care of patients with dystrophic epidermolysis bullosa with ocular surface involvement,” Vetencourt and colleagues wrote, acknowledging that larger studies and longer follow-up are needed.

A rare genetic disease caused by variants in COL7A1, which encodes type VII collagen, dystrophic epidermolysis bullosa produces blistering and scarring of the ocular surface, and can lead to blindness. Traditional treatment has involved wound management and supportive care.

B-VEC is a replication-deficient HSV-1-based gene therapy engineered to deliver functional human type VII collagen, which was approved by the FDA last May for the treatment of wounds in patients at least 6 months of age with COL7A1-mutated dystrophic epidermolysis bullosa.

A similar gene therapy approach has been beneficial in controlling diabetic retinopathy with a single injection of vascular endothelial growth factor (VEGF)-targeted RGX-314. This therapy helps reduce the formation of leaky blood vessels and has been investigated in other retinal conditions such as macular edema.

Ophthalmologist Matthew Gorski, MD, of Northwell Health in New Hyde Park, New York, told MedPage Today that “the result noted in this one case is interesting, since it would really be the first type of drop to directly treat this genetic disease process.”

While the results are exciting, he urged caution since the outcome was observed in a single patient. “We cannot just assume that it would work for most patients,” he said.

In theory, however, the science behind these results make the therapy “a promising option for patients with dystrophic epidermolysis bullosa, although many further clinical trials are necessary to determine whether this is an effective treatment in a larger population,” Gorski said. “Future studies have to make sure the drop is safe without serious side effects, in addition to confirming whether the therapy is effective for many patients.”

The patient in the case report was first seen at Bascom Palmer at age 4. He had contractures of the arms and legs and syndactyly of the hands and fingers owing to his generalized dystrophic epidermolysis bullosa-related wounds. His entire body was wrapped in elastic bandages with the exception of his face and neck.

At initial presentation, his best-corrected visual acuity was 20/40 (logMAR 0.30) in the right eye and 20/80 (logMAR 0.60) in the left eye. He underwent two surgeries for symblepharon followed by medical treatment, but symblepharon recurred.

At age 5, the patient presented with ankyloblepharon and hand-motion visual acuity (logMAR 3.00) in the left eye. Three months after the second surgery in 2016, visual acuity in his left eye stabilized at approximately 20/400 (logMAR 1.30), but his right eye continued to deteriorate.

In 2020, the patient enrolled in a phase III trial of B-VEC, which improved generalized full-wound healing. On hypothesis is that B-VEC might mitigate his severe recurrent ocular surface involvement, he was cleared for ocular therapy on a compassionate-use basis.

Three months after surgery on his right eye and after regular use of topical B-VEC (19 cumulative doses), full healing of the corneal epithelium was achieved.

“The degree of improvement that we observed was remarkable, given the lack of change in the contralateral eye, which underwent similar treatment but without the ophthalmic application of B-VEC,” Vetencourt and colleagues wrote.

Before surgery, the intraocular pressure of the patient’s right eye was 16 mm Hg, and after surgery it remained within normal limits, ranging from 9 to 18 mm Hg. After 8 months of topical B-VEC (24 doses), funduscopic examination revealed no retinal abnormalities.

Although B-VEC was well-tolerated, the boy experienced a non-ocular serious adverse event in the form of complications after gastrointestinal surgery performed concurrently with symblepharon surgery, which led to hospitalization for vomiting. His B-VEC treatment, however, was not interrupted and he was discharged without sequelae.

Among the case study’s limitations, the authors noted the lack of a molecular or genetic analysis of corneal epithelial cells before or after the surgery and B-VEC application and the lack of an untreated control eye and a natural history after the intervention in the treated eye for comparison. They also cited the potential contribution of other concomitant medications given after surgery and the absence of formal assessments of eye pain, although the child reported no significant eye pain before or after B-VEC.

  • author['full_name']

    Diana Swift is a freelance medical journalist based in Toronto.

Disclosures

Krystal Biotech provided compassionate-use B-VEC.

Vetencourt had no competing interests to declare.

Several co-authors reported employment at or stock ownership in Krystal Biotech, as well as other ties to the pharmaceutical industry.

Gorski disclosed no competing interests relevant to his comments.

Primary Source

New England Journal of Medicine

Source Reference: Vetencourt AT, et al “Ocular gene therapy in a patient with dystrophic epidermolysis bullosa” N Engl J Med 2024; DOI: 10.1056/NEJMoa2301244.

Source link

Share this Article
Leave a comment
adbanner