Credit: US Food and Drug Administration

The US Food and Drug Administration (FDA) announced its approval of a treatment known as beremagene geperpavec (B-VEC) (VYJUVEK), a modified herpes simplex virus type 1 vector designed for patients with dystrophic epidermolysis bullosa (DEB).¹

The PDUFA date for the treatment had been extended to May of 2023 due to a regulatory update that the FDA deemed necessary. Krystal Biotech, Inc. had submitted a manufacturing information update regarding a replaced hardware unit in the treatment’s manufacturing process.²

DEB—also known as “butterfly disease”—is an uncommon genetic skin condition caused by mutations in the COL7A1 gene. This disorder leads to individuals experiencing severe skin fragility, making them susceptible to injuries from minor contact in their daily lives.

The rare skin condition—a subtype of epidermolysis bullosa—is less well-known in the by the public in general and is estimated to affect around 1 in 25,000 to 50,000 people across the world.2 DEB causes patients’ skin to be fragile and to easily blister as a result of minor touches or friction such as rubbing or scratching.³

“The signs and symptoms of dystrophic epidermolysis bullosa vary widely among affected individuals,” writes the National Center for Advancing Translational Sciences. “In mild cases, blistering may primarily affect the hands, feet, knees, and elbows. Severe cases of this condition involve widespread blistering that can lead to vision loss, scarring, and other serious medical problems.”⁴

B-VEC is a promising approach to DEB, and is created by altering an HSV-1 vector. Within this modified vector, 2 copies of the COL7A1 coding sequence are inserted. The gene delivery mechanism enables the viral DNA to transcribe and translate into C7, which is then secreted into the extracellular space.

“This is a devastating disease,” said M. Peter Marinkovich, M.D., primary investigator of the GEM-3 trial, Director of the Blistering Disease Clinic at Stanford Health Care and Associate Professor of Dermatology at the Stanford University School of Medicine. “Until now, doctors and nurses had no way to stop blisters and wounds from developing on dystrophic EB patient skin and all we could do was to give them bandages and helplessly watch as new blisters formed. VYJUVEK topical gene therapy changes all of this. 

"VYJUVEK both heals patient wounds and prevents skin from re-blistering because it actually corrects the underlying skin defect of dystrophic EB. Because it’s safe and easy to apply directly to wounds, it doesn't require a lot of supporting technology or specialized expertise, making VYJUVEK highly accessible even to patients who live far away from specialized centers."

Marinkovich works as an associate professor of dermatology at Stanford University School of Medicine, had presented the late-breaking phase 3 data on B-VEC at the American Academy of Dermatology (AAD) 2022 Annual Meeting in 2022.

Prior to the PDUFA date announcement, phase 3 trial on 31 DEB patients showed that approximately 70% of wounds had closed within 6 months of treatment, including the patient included with the dominant form of the condition.⁵

Comparatively, the placebo group in this trial had a closure rate of about 20%. The study’s research team also observed that patients who received B-VEC therapy exhibited 50% wound healing durability, defined as complete closure at both 3 months and 6 months, in contrast to only 7% of those who received the placebo.

“You use (B-VEC) on an outpatient basis, you can just use it in the clinic to treat these patients’ wounds,” Marinkovich noted. “I think it’s really a cutting-edge type of therapy that, if everything goes well, may be approved in a year or so.”⁶

The FDA’s decision is an impactful step towards treatment of the debilitating skin condition.

References

1. ^{Krystal Biotech receives FDA approval for the first-ever redosable gene therapy, VYJUVEKTM (Beremagene Geperpavec-svdt) for the treatment of dystrophic epidermolysis bullosa. Krystal Biotech. (2023, May 19). https://ir.krystalbio.com/news-releases/news-release-details/krystal-biotech-receives-fda-approval-first-ever-redosable-gene}
2. ^{Smith T. FDA Extends PDUFA Date for B-VEC Gene Therapy for Dystrophic Epidermolysis Bullosa. HCPLive. January 12, 2023. Accessed May 19, 2023. https://www.hcplive.com/view/fda-extends-pdufa-date-b-vec-gene-therapy-dystrophic-epidermolysis-bullosa}
3. ^{Stanford Medicine Dermatology. Epidermolysis Bullosa Frequently Asked Questions. Stanford Medicine Dermatology website. Accessed May 19, 2023. https://med.stanford.edu/dermatology/resources/gsdc/eb_clinic/eb-faqs.html.}
4. ^{National Institutes of Health. Dystrophic Epidermolysis Bullosa. Office of Rare Diseases Research website. Accessed May 19, 2023. https://rarediseases.info.nih.gov/diseases/2150/dystrophic-epidermolysis-bullosa.}
5. ^{Smith T. Dystrophic Epidermolysis Bullosa: Positive Results from Topical Gene Therapy. HCPLive. January 3, 2023. Accessed May 19, 2023. https://www.hcplive.com/view/dystrophic-epidermolysis-bullosa-positive-results-topical-gene-therapy.}
6. ^{Kunzumann K. Topical Gene Therapy B-VEC Reaches Phase 3 Efficacy Endpoints for DEB Disease Reversal. March 26, 2022. Accessed May 19, 2023. https://www.hcplive.com/view/topical-gene-therapy-b-vec-phase-3-efficacy-endpoints-deb-disease-reversal.}