Krystal Reports Positive Topline Results from Pivotal Trial of DEB Therapy

Krystal Biotech reported positive topline results from its pivotal GEM-3 trial of its experimental therapy Vyjuvek for the treatment of dystrophic epidermolysis bullosa, a rare skin condition.

“Dystrophic epidermolysis bullosa is referred to as ‘the worst disease you’ve never heard of’ because of the incredibly devastating reality that patients with this genetic condition face, and we are thrilled to announce positive results from our pivotal GEM-3 trial of Vyjuvek which showed that this topical gene therapy led to durable wound healing in dystrophic EB wounds,” said Suma Krishnan, founder and chief operating officer of Krystal. “With these results in hand, we look forward to advancing discussions with regulatory authorities and will work quickly to bring this potential first-ever treatment to patients with dystrophic EB and their families who are in desperate need.”

Dystrophic epidermolysis bullosa (DEB) is a rare and severe monogenic disease that affects the skin and mucosal tissues. It is caused by one or more mutations in a gene called COL7A1, which is responsible for the formation of the protein type VII collagen protein (COL7) that forms anchoring fibrils that bind the dermis (inner layer of the skin) to the epidermis (outer layer of the skin). The lack of functional anchoring fibrils leads to extremely fragile skin that blisters and tears from minor friction or trauma. DEB patients suffer from open wounds, which lead to skin infections, fibrosis which can cause fusion of fingers and toes, and ultimately an increased risk of developing squamous cell carcinoma, which in severe cases can be fatal.

Vyjuvek is an experimental, non-invasive, topical gene therapy designed to deliver two copies of the COL7A1 gene when applied directly to DEB wounds. Unlike the current standard of care, Vyjuvek was designed to treat DEB at the molecular level by providing the patient’s skin cells the template to make normal COL7 protein, thereby addressing the fundamental disease-causing mechanism.

The U.S. Food and Drug Administration and the Europeans Medicines Agency have each granted Vyjuvek orphan drug designation for the treatment of DEB, and the FDA has granted Vyjuvek fast track designation and rare pediatric designation for the treatment of DEB. In addition, in 2019, the FDA granted Regenerative Medicine Advanced Therapy to Vyjuvek for the treatment of DEB and the EMA granted Priority Medicines eligibility for Vyjuvek to treat DEB.

The primary endpoint of the trial evaluated complete wound healing of topical Vyjuvek compared to placebo at six-month timepoints and met statistical significance. Vyjuvek is the first non-invasive, topical and redosable gene therapy in development, and the only genetically corrective approach to treat dystrophic EB that has successfully completed a double blinded phase 3 trial.

A total of 31 patients (31 primary matched-wound pairs) were enrolled and evaluable for safety and efficacy per the primary intent-to-treat analysis. Some 67 percent of wounds treated with Vyjuvek achieved the primary endpoint of investigator assessed complete wound healing at the six-month timepoints as compared to 22 percent of wounds treated with placebo.

A total of 71 percent of wounds treated with Vyjuvek achieved the secondary endpoint of investigator assessed complete wound healing at the three-month timepoints as compared to 20 percent of wounds treated with placebo.

In an ad-hoc analysis, the trial also demonstrated a statistical difference between the active and placebo groups for wounds that demonstrated complete wound healing at both the three- and six-month timepoints.

Vyjuvek was well tolerated. No drug-related serious adverse events or discontinuations due to treatment were reported. One mild drug-related adverse event was reported during the trial.

Based on these results, Krystal intends to file an application with the FDA in the first half of 2022 for approval to market Vyjuvek. The company expects to submit an application for European approval shortly after that.

Author: Rare Daily Staff