Gene Therapy Yields Complete Wound Healing in Dystrophic Epidermolysis Bullosa


The phase 3 GEM-3 study met both its primary and secondary end points compared with placebo in dEB.

Krystal Biotech’s investigational gene therapy beremagene geperpavec (B-VEC, Vyjuvek) improved wound healing in patients with dystrophic epidermolysis bullosa (dEB), according to topline results from the placebo-controlled phase 3 GEM-3 trial (NCT04491604).

“Dystrophic epidermolysisbullosa 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, Krystal Biotech, in a statement. “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.”

B-VEC is designed to deliver 2 copies of the COL7A1 gene when applied directly to dEB wounds. The therapy was investigated in thedouble-blind GEM-3 trial which met both its primary endpoint of complete wound healing in 6 months and its secondary endpoint of complete wound healing at 3 months compared with placebo. The therapy was well-tolerated in treated participants and no treatment-related serious adverse events (AEs) were observed. 

The trial included 31 participants with dEBin the intent-to-treat analysis.These participants ranged in age from 1 to 44 years. Complete wound healing at 6 months was observed in 67% of B-VEC-treated wounds compared with 22% of placebo-treated wounds (absolute difference, 45.8% [95% CI, 23.6-68.0]; P <.005). Complete wound healing at 3 months was observed in 71% of B-VEC-treated wounds compared with 20% of placebo-treated wounds (absolute difference, 51.0% [95% CI, 29.3-72.6]; P <.005).

READ MORE: FDA Grant Supports Recessive Dystrophic Epidermolysis Bullosa Gene Therapy Study

“Today’s positive B-VEC results represent the culmination of years of study on the molecular basis and genetic correction of this disease. Finally, dystrophic EB patients may have an easily administered genetically targeted therapy which has been shown to promote durable wound healing in this clinical trial. This is a long overdue milestone for patients living with this disease, and one that has potential to drastically change the treatment paradigm,” Peter Marinkovich, MD, director, Bullous Disease Clinic, and associate professor of dermatology, Stanford University, added to the statement.

B-VEC was well-tolerated, with no serious treatment-related AEs or discontinuations reported. One mild, treatment-related AE was reported. No meaningful change in anti-HSV-1 or anti-COL7 antibodies was reported and immunogenicity profile was consistent with the phase 2 GEM-1/2 study (NCT03536143). Trial participants were followed upwith30 days after the last dosing at week 26 and were invited to enroll in a long-term safety, ppen-labelextension study (NCT04917874).

B-VEC was previously granted orphan drug designation by both the FDA and EMA as well as fast track, rare pediatric, and regenerative medicine advanced therapy designations by the FDA and PRIorityMEdicines designation by the EMA. Krystal Biotech plans to submit a biologics license application to the FDA for B-VEC in the first half of 2022.

“We founded Krystal less than six years ago with the goal of developing a non-invasive, genetically corrective therapy for dystrophic EB. We offer our deepest gratitude to the patients, caregivers, investigators, and of course to the broader Krystal team who worked tirelessly to help us reach this exciting moment in the progression of the VyjuvekTM program,” Krishnan added. “These pivotal data provide important validation of our redosable gene delivery technology, emboldening us to expand our pipeline to address other genetic skin diseases, continue to explore the potential in genetic lung diseases, and invest in growing the platform capability to address new organ systems as well.”

Krystal Biotech announces positive topline results from GEM-3 pivotal trial of VYJUVEK™ in patients with dystrophic epidermolysis bullosa. News release. Krystal Biotech. November 29, 2021.
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