Dystrophic Epidermolysis Bullosa Gene Therapy BLA Accepted With Priority Review


The BLA was supported by data from 2 intrapatient, placebo-controlled clinical trials.

The FDA has accepted for filing a biologics license application (BLA) for Krystal Biotech's B-VEC, an investigational, redosable gene therapy for the treatment of dystrophic epidermolysis bullosa (DEB).1 The BLA was accepted with priority review, with a PDUFA action date of February 17, 2023.

The BLA was supported by data from 2 intrapatient, placebo-controlled clinical trials: the phase 2 GEM-1/2 (NCT03536143) study and the phase 3 GEM-3 study (NCT04491604).

"We are delighted to receive the FDA's acceptance of our BLA submission and move one step closer to potentially bringing a medicine to fundamentally treat DEB patients," Suma Krishnan, co-founder and president, research and development, Krystal Biotech, said in a statement.1 "We are committed to working closely with the FDA to bring this potential, first-ever treatment to patients living with DEB as quickly as possible."

B-VEC is intended for topical application directly to DEB wounds and delivers 2 functional copies of the disease-targeted gene, COL7A1, to allow the skin cells to produce the normal COL7 protein. B-VEC previously received orphan drug designation from both the FDA and the European Medicines Agency (EMA) and fast track designation and rare pediatric disease designation from the FDA.

The open-label GEM-1/2 trial enrolled 9 patients with recessive DEB and demonstrated that repeated applications of B-VEC to DEB wounds was well-tolerated and associated with durable wound closure and full-length COL7 expression.2 A paper reporting the results of the study published in Nature Medicine noted that no grade 2 or greater drug-related adverse events, vector shedding, or tissue-bound skin immunoreactants were observed, and end points related to COL7 expression, anchoring fibril assembly, wound surface area reduction, duration of wound closure, and time to wound closure after B-VEC treatment were met.3 However, the investigators chose to abandon the planned assessment of patient-reported pain severity due to the small proportion of wounds treated. Ultimately, first author Irina Gurevich, PhD, and colleagues concluded that B-VEC was well-tolerated, easily-administered, and capable of promoting wound healing in patients with recessive DEB.

The double-blind, multicenter GEM-3 trial enrolled 31 patients between the ages of 1 and 44 years and demonstrated that B-VEC was generally well-tolerated, with no drug-related serious adverse events observed.4,2 The study met its primary end point related to complete wound healing at 6 months and its secondary end point related to complete wound healing at 3 months.2 Data from the GEM-3 study were presented earlier this year at the American Academy of Dermatology (AAD) 2022 Annual Meeting, March 25-29, in Boston, Massachusetts, and were summarized in previous coverage by CGTLive.

“It may be the case that more dermatologists will be seeing these patients, because the therapy is such an easy therapy to use,” Peter Marinkovich, MD, associate professor of dermatology at Stanford University School of Medicine, the primary investigator who presented the data at the AAD meeting, said regarding B-VEC in a March 2022 interview with our sister site, HCPLive. “You use it at an outpatient basis, you can just use it in the clinic to treat these patients’ wounds. I think it’s really a cutting-edge type of therapy that, if everything goes well, may be approved in a year or so.”

Krystal Biotech plans to submit a marketing authorization application for B-VEC to the EMA before the end of 2022.1

1. FDA accepts Krystal Biotech’s biologics license application for dystrophic epidermolysis bullosa. News release. Krystal Biotech, Inc. August 18, 2022. https://ir.krystalbio.com/news-releases/news-release-details/fda-accepts-krystal-biotechs-biologics-license-application
2. Krystal Biotech submits biologics license application to U.S. FDA seeking approval of B-VEC for the treatment of patients with dystrophic epidermolysis bullosa. Krystal Biotech, Inc. June 22, 2022. https://ir.krystalbio.com/news-releases/news-release-details/krystal-biotech-submits-biologics-license-application-us-fda 
3. Gurevich I, Agarwal P, Zhang P, et al. In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial. Nat Med. 2022;28(4):780-788. doi.org/10.1038/s41591-022-01737-y
4. Marinkovich MP, Gonzalez ME, Guide S, et al. GEM-3: A phase 3 study of beremagenegeperpavec (B-VEC), an investigational, topical gene therapy, for the treatment of dystrophic epidermolysis bullosa (DEB). Presented at: AAD 2022 Annual Meeting, March 25-29, Boston, Massachusetts.

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