FDA Approves First-Ever Redosable Gene Therapy for the Treatment of Dystrophic Epidermolysis Bullosa

Rare Daily Staff

The U.S. Food and Drug Administration approved Krystal Biotech’s redosable gene therapy Vyjuvek for the treatment of patients six months of age or older with dystrophic epidermolysis bullosa.

“Today’s landmark approval of Vyjuvek as the first redosable gene therapy ushers in a whole new paradigm to treat genetic diseases and is an important milestone for patients affected by DEB as well as their families and caregivers,” said Krish Krishnan, chairman and CEO of Krystal Biotech.

Dystrophic epidermolysis bullosa (DEB) is a rare and serious disease that affects the skin and mucosal tissues caused by one or more mutations in the COL7A1 gene. The COL7A1 gene is responsible for the production of functional COL7 protein that forms anchoring fibrils necessary to bind the dermis (inner layer of the skin) to the epidermis (outer layer of the skin). The lack of functional anchoring fibrils in DEB patients leads to extremely fragile skin that blisters and tears with minor friction or trauma. DEB patients suffer from open wounds, which lead to recurrent skin infections and fibrosis that can cause fusion of fingers and toes, and ultimately increase the risk of developing an aggressive form of skin cancer.

Vyjuvek, which uses an engineered herpes simplex virus to deliver a gene that’s much larger than the standard viral vectors, is designed to address the genetic root cause of DEB by delivering functional copies of the human COL7A1 gene to provide wound healing and sustained functional COL7 protein expression with redosing. Vyjuvek is the first-ever redosable gene therapy and the first and only medicine approved by the FDA for the treatment of DEB, both recessive and dominant, that can be administered by a healthcare professional in either a healthcare professional setting or in the home.

“This is a devastating disease,” said M. Peter Marinkovich, 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.”

The FDA approval of Vyjuvek is based on two clinical studies. The GEM-1/2 trial was an intra-patient, open label, single center, randomized, placebo-controlled study showing that repeat topical applications of Vyjuvek were associated with durable wound closure, full-length cutaneous COL7 expression, and anchoring fibril assembly with minimal reported adverse events. The GEM-3 trial was an intra-patient, double-blinded, multi-center, randomized, placebo-controlled study that met both its primary endpoint of complete wound healing at six months and its key secondary endpoint of complete wound healing at three months. Vyjuvek was well tolerated with no drug-related serious adverse events or discontinuations due to treatment-related events.

“Data from our GEM-1/2 trial and our GEM-3 trial, published in Nature Medicine and the New England Journal of Medicine, respectively, demonstrated the strength of both studies showing that Vyjuvek safely and effectively improved wound healing,” said Suma Krishnan, president, Research & Development, Krystal Biotech. “For so many years, all we have been able to offer DEB patients was palliative care, but now, based on the strength of the company’s clinical trial data, there is a safe and effective FDA approved treatment.”

Vyjuvek is expected to be available in the United States in the third quarter of 2023, and the company will begin the promotion of Vyjuvek immediately. With this approval, the FDA issued the company a Rare Pediatric Disease Priority Review Voucher (PRV), which confers priority review to a subsequent drug application that would not otherwise qualify for priority review. The PRV program is designed to encourage the development of new drugs for the prevention or treatment of rare diseases.

Fresh on the heels of the approval, Krystal Biotech entered into a securities purchase agreement for the sale of 1,729,729 shares of its common stock at $92.50 per share in a private placement to certain qualified institutional buyers for gross proceeds of approximately $160 million, before deducting any offering-related expenses.

“These additional funds, together with our existing cash, cash equivalents and investments, should allow us to fund the Vyjuvek launch, future operations, and the advancement of our growing pipeline through the end of 2026, said Krish Krishnan, chairman and CEO of Krystal Biotech. “It also allows us to retain the optionality of monetizing the Priority Review Voucher we received in connection with the FDA approval of Vyjuvek at a future date with favorable terms and without any dilution.”

Photo: Krish Krishnan, chairman and CEO of Krystal Biotech