B-VEC Shows Quality of Life Improvements in Dystrophic Epidermolysis Bullosa

Krystal Biotech's investigational topical gene therapy has shown promise in DEB. It is designed to deliver COL7A1 and restore C7 protein in patients with the rare disorder.

Isin Sinem Bagci, MD, a research scientist in dermatology operations at Stanford University School of Medicine

Isin Sinem Bagci, MD

A version of this interview originally appeared on our sister site, DermatologyTimes.

At the at the 2023 Annual Meeting of the American Academy of Dermatology (AAD) in New Orleans, Louisiana, data from a recent study of beremagene geperpavec (B-VEC; Krystal Biotech) as a treatment for patients with dystrophic epidermolysis bullosa (DEB) were presented suggesting the therapy may improve patient quality of life.1,2 Ultimately, B-VEC was more likely to be associated with complete wound healing than placebo.

Based on the findings, Krystal Biotech had announced a home dosing extension study in April 2022, study investigator Isin Sinem Bagci, MD, a research scientist in dermatology operations at Stanford University School of Medicine, who presented the data, said. Meanwhile, the therapy's application to the FDA has a PDUFA expected in May 2023 after a 3-month extension was issued by the agency in January.3

At AAD, Bagci noted that she and her colleagues set a high bar for the primary end point (complete wound healing at 6 months) and secondary end point (complete wound healing at 3 months).2 Based on these data, Bagci said in her presentation that “a redosable/in vivo/topical gene therapy [would be] emerging this year in the genetic disease field."

Over a 26-week period, 2 wounds on each patient that were of similar size, anatomical region, and appearance were randomly assigned to receive application of B-VEC or placebo once weekly until the wound closed. If the wound reopened, treatment was resumed. A response was defined as at least 2 consecutive weeks of wound healing with total wound closure necessary for wounds to be deemed healed.

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“The results were quite impressive,” Bagci said. Complete wound healing was reported for 67% of the wounds exposed to B-VEC, in comparison with 22% of those exposed to placebo (95% CI, 24-68; P = .002). At 3 months, 71% of the wounds treated with B-VEC were deemed completely healed as opposed to 20% of those wounds exposed to placebo (95% CI, 29 to 73; P <.001). “Younger patients had a better treatment response than older patients, so it’s important to start the treatment early," Bagci said.

Dystrophic Epidermolysis Bullosa (DEB)

  • DEB is a rare genetic disorder that affects the skin and mucous membranes, causing blistering and skin fragility.
  • The condition is caused by mutations in the COL7A1 gene, which is responsible for producing type 7 collagen, an important component of the skin's anchoring fibrils.
  • DEB can be inherited in an autosomal dominant or autosomal recessive pattern, depending on the specific mutation involved.
  • There is currently no cure for DEB, and treatment primarily focuses on managing symptoms and preventing complications such as infection and scarring.
  • Treatment options may include wound care, pain management, nutritional support, and physical therapy.

Bagci et al also found that B-VEC had positive effects on larger and chronic wounds. One such patient, a 21 year old with a large (>100 cm2) wound on his back for longer than a decade that "was “decreasing his quality of life," was able to shower and lay on their back without significant pain. The wound has remained closed for more than a year, and quality of life has improved in parallel, Bagci explained.

Adding to the hopeful news was the safety results, Bagci said. Of the 45 reported adverse events (AEs), 58% were considered mild and 48% moderate. Only 1 AE (mild erythema) was considered related to B-VEC, and no AEs led to discontinuation in either group. Bagci said 3 patients experienced 5 serious AEs, but none were 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.

DEB is caused by mutations in COL7A1, a gene involved in assembling type 7 collagen and plays a crucial role in stabilizing the skin, and there are no currently approved corrective therapies. B-VEC is a topical investigational herpes simplex virus type 1-based gene therapy that delivers COL7A1 and therefore restores C7 protein. B-VEC has previously received orphan drug designation, fast track designation, and rare pediatric designation, and Regenerative Medicine Advanced Therapy by the FDA.

1. 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
2. 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.
3. Krystal Biotech announces FDA’s 3-month extension of BLA PDUFA date and regulatory update for B-VEC to treat patients with dystrophic epidermolysis bullosa. News release. Krystal Biotech, Inc. January 9, 2023. Accessed March 27, 2023. https://ir.krystalbio.com/news-releases/news-release-details/krystal-biotech-announces-fdas-3-month-extension-bla-pdufa-date
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