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Investigational Gene Therapy Expected to Improve QoL for Patients With DEB


Designed to address the underlying causes of DEB, the investigational topical gene therapy shows great promise to improve quality of life for patients with this rare disorder.

DNS Helix im Reagenzglas. Generative AI credit: Alexander Limbach Adobestock

Alexander Limbach/Adobestock

There is a promising treatment on the horizon for patients with dystrophic epidermolysis bullosa (DEB), according to Isin Sinem Bagci, MD, a presenter in the “New Technologies of Dermatological Science and Practice” session at the 2023 Annual Meeting of the American Academy of Dermatology in New Orleans, Louisiana.1

Bagci, who is a research scientist in dermatology operations at Stanford University School of Medicine, highlighted data from a recent study of beremagene geperpavec (B-VEC) for DEB.2 Bagci was one of the investigators on that study, which found that B-VEC was more likely associated with complete wound healing in comparison with placebo. Based on this data, Bagci expected “a redosable/in vivo/topical gene therapy [would be] emerging this year in the genetic disease field,” she told attendees.

DEB is caused by mutations in COL7A1, a gene involved in assembling type 7 collagen and plays a crucial role in stabilizing the skin, Bagci explained. As a result, patients with DEB have blisters and scars over much of their bodies. B-VEC is a topical investigational herpes simplex virus type 1-based gene therapy that delivers COL7A1 and therefore restores C7 protein. Because there are no currently approved corrective therapies for DEB, B-VEC’s success to date brings hope for many patients, she said. For the treatment of DEB, B-VEC received orphan drug designation, was granted fast track designation and rare pediatric designation, and was granted Regenerative Medicine Advanced Therapy by the US Food and Drug Administration.

The results from this phase 3, double blind, intrapatient randomized, placebo-controlled trial were published in The New England Journal of Medicine, Bagic said.2 She explained participants included adults and children at least 6 months old with genetically confirmed clinical diagnosis of DEB and were recruited across 3 US sites. Although participants from phase 1 and 2 trials were not excluded, patients were excluded if they were actively receiving treatment with immunotherapy, chemotherapy, or other investigations agents. Evidence or history of squamous cell carcinoma and infections disqualified wound sites.

Over a 26-week period, 2 wounds on each patient that were of similar size, anatomical region, and appearance were randomized to receive application of B-VEC or placebo once per week until the wound closed (treatment was resumed if the wound reopened). Response was defined as at least 2 consecutive weeks of wound healing; total wound closure was required for wounds to be considered healed. Bagci noted she and her colleagues set a high bar for the primary end point, which was complete wound healing at 6 months; secondary end point was complete wound healing at 3 months. Bagci said safety end points looked at adverse events.

“The results were quite impressive,” she told attendees. Complete wound healing occurred in 67% of the wounds exposed to B-VEC, in comparison to 22% of those exposed to placebo. Similarly, she noted 71% of the wounds were deemed completely healed at 3 months for those exposed to B-VEC as opposed to 20% of those wounds exposed to placebo.

Subgroup analysis also uncovered some interesting data, Bagci reported. “Younger patients had a better treatment response than older patients,” she said, “so it’s important to start the treatment early.”

Bagci and colleagues also found B-VEC had positive effects on larger and chronic wounds. She shared the example of a 21 year old patient who had a large (>100 cm2) wound on his back for more than 10 years. “It was decreasing his quality of life; it was a major problem,” she told attendees.

After treatment, she said the patient reportedly could shower as well as lay on their back without significant pain. The wound has remained closed for more than a year, and the patient reports increased quality of life.

Adding to the hopeful news was the safety results, Bagci said. Of the 45 reported adverse events, 58% were considered mild and 48% were considered moderate. She added only 1 adverse event (mild erythema) was considered related to B-VEC, and no adverse events led to discontinuation of either B-VEC or placebo. Bagci said 3 patients experienced 5 serious adverse events, but they were not related to B-VEC or placebo. In addition, a post-hoc analysis found B-VEC treatment response was not associated with baseline HSV-1 serostatus or C7 seroconversion.

Based on the data, Krystal Biotech announced a home dosing extension study in April 2022, she said. The doses would be administered by a health care provider and would be a convenience for patients.

Meanwhile, Bagci said she is looking forward to good news about B-VEC later this year, with the PDUFA expected in May 2023.

Are you attending the annual meeting? Share your highlights with us via email: DTEditor@mmhgroup.com.


1. Bagci IS. Gene therapy of the skin and its integration into clinical practice. Presented at the 2023 Annual Meeting of the American Academy of Dermatology. March 17-21; New Orleans, Louisiana.

2. Guide SV, Gonzalez ME, Bağcı IS, et al. Trial of beremagene geperpavec (B-VEC) for dystrophic epidermolysis bullosa. N Engl J Med. 2022;387(24):2211-2219. doi:10.1056/NEJMoa2206663

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