Positive Results from Open Label Extension Study of First-Ever Topical Gene Therapy |AAD 2024

An open label extension study of a novel topical gene therapy for a rare skin disease that causes blistering wounds showed that the therapy continues to work to keep wounds closed and scores well on measurements of patient satisfaction and quality of life, according to data presented today at the annual meeting of the American Academy of Dermatology.

Amy Paller, M.D., M.S.

Amy S. Paller, M.D., M.S., showed pictures of patient wounds at the baseline of the phase 3 trial that led to the drug’s approval, at the end of the phase 3 trial, and at the end of the open-label extension study.

“I think what you can notice is that while there was improvement in the end of phase 3, there was even more improvement by the end of the open- label study in these patients,” said Paller, who is chair of the dermatology department at the Northwestern University Feinberg School of Medicine in Chicago.

Paller’s presentation was one of 18 during the three-hour session devoted to late-breaking abstracts.

The FDA announced that it had approved the topical gene therapy, Vyjuvek (beremagene geperpavec) in May 2023. The approval was based on favorable phase 3 trial results that published in December 2022 in The New England Journal of Medicine.

Vyjuvek is used to treat dystrophic epidermolysis bullosa, a rare genetic disorder that affects the fibrils that attach the epidermis to the underlying dermis. People with the disease experience blistering and wounds from even minor trauma because the layers of their skin are not properly attached by the fibrils. Repeated blistering can lead to squamous-cell carcinoma and infections. Dystrophic epidermolysis bulbosa is caused by mutations in the COL7A1 gene, which encodes type VII collagen (COL7), a protein that makes up the fibrils. Vyjuvek uses a herpes simplex virus type 1 to deliver nonmutated COL7A1 genes into skin to make COL7. The gene-bearing herpes simplex virus is mixed into a gel and droplets of the gel are daubed on the wound on a weekly basis by a healthcare professional.

Results of the 26-week trial that led to Vyjuvek’s FDA approval showed that after six months of treatment, 65% of the wounds treated with the topical gene therapy were completely closed compared with 26% in the placebo group, Paller said. Moreover, the safety data didn’t show any major problems, she said, and no one discontinued treatment because of an adverse event.

The open-label study included patients who switched from treatment with a placebo in the phase 3 trial to treatment with Vyjuvek. Paller said one of the reasons for the study was to continue to provide access to Vyjuvek to those who were successfully treated with the topical gene therapy during the phase 3 trial. The open label trial ran from May 2021 through July 2023 when the drug became commercially available. A total of 47 patients participated, although five dropped out for reasons unrelated to treatment. Approximately 60% of the study participants in the open label extension trial were treated with Vyjuvek for more than a year, and one patient was treated for 2.2 years. One patient had two incidents of bleeding from wounds that might have been related to treatment with Vyjuvek; otherwise, Paller said, the open-label extension study did not yield data suggesting safety problems.

Paller said the wound closure rates in the open-label study were consistent with those in the phase 3 study and that wounds that were closed tended to stay that way. “The fact that [these wounds] stayed closed was really very important to these patients,” she said.

Results were favorable from the structured questionnaires designed to assess patient satisfaction and quality of life, Paller said. They showed high treatment satisfaction and a trend toward improved quality of life, she said.