• Shireen V Guide, Mercedes E Gonzalez, I Sinem Bağcı, Brittani Agostini, Hubert Chen, Gloria Feeney, Molly Steimer, Binoy Kapadia, Kunju Sridhar, Lori Quesada Sanchez, Franshesca Gonzalez, Matthew Van Ligten, Trevor J Parry, Surya Chitra, Lisa A Kammerman, Suma Krishnan, and M Peter Marinkovich.
• From the Mission Dermatology Center, Department of Dermatology, Children's Hospital of Orange County, University of California Irvine, Rancho Santa Margarita (S.V.G., M.V.L.), the Department of Dermatology, Stanford University School of Medicine, Stanford (I.S.B., K.S., M.P.M.), and the Veterans Affairs Medical Center, Palo Alto (M.P.M.) - all in California; Pediatric Skin Research, Coral Gables, FL (M.E.G., L.Q.S., F.G.); Krystal Biotech, Pittsburgh (B.A., H.C., G.F., M.S., B.K., T.J.P., S.K.); Savio Group Analytics, Hockessin, DE (S.C.); and Kammerman Consulting, Chevy Chase, MD (L.A.K.).
• N. Engl. J. Med. 2022 Dec 15; 387 (24): 221122192211-2219.

BackgroundDystrophic epidermolysis bullosa is a rare genetic blistering skin disease caused by mutations in COL7A1, which encodes type VII collagen (C7). Beremagene geperpavec (B-VEC) is a topical investigational herpes simplex virus type 1 (HSV-1)-based gene therapy designed to restore C7 protein by delivering COL7A1.MethodsWe conducted a phase 3, double-blind, intrapatient randomized, placebo-controlled trial involving patients 6 months of age or older with genetically confirmed dystrophic epidermolysis bullosa. For each patient, a primary wound pair was selected, with the wounds matched according to size, region, and appearance. The wounds within each pair were randomly assigned in a 1:1 ratio to receive weekly application of either B-VEC or placebo for 26 weeks. The primary end point was complete wound healing of treated as compared with untreated wounds at 6 months. Secondary end points included complete wound healing at 3 months and the change from baseline to weeks 22, 24, and 26 in pain severity during changes in wound dressing, assessed with the use of a visual analogue scale (scores range from 0 to 10, with higher scores indicating greater pain).ResultsPrimary wound pairs were exposed to B-VEC and placebo in 31 patients. At 6 months, complete wound healing occurred in 67% of the wounds exposed to B-VEC as compared with 22% of those exposed to placebo (difference, 46 percentage points; 95% confidence interval [CI], 24 to 68; P = 0.002). Complete wound healing at 3 months occurred in 71% of the wounds exposed to B-VEC as compared with 20% of those exposed to placebo (difference, 51 percentage points; 95% CI, 29 to 73; P<0.001). The mean change from baseline to week 22 in pain severity during wound-dressing changes was -0.88 with B-VEC and -0.71 with placebo (adjusted least-squares mean difference, -0.61; 95% CI, -1.10 to -0.13); similar mean changes were observed at weeks 24 and 26. Adverse events with B-VEC and placebo included pruritus and chills.ConclusionsComplete wound healing at 3 and 6 months in patients with dystrophic epidermolysis bullosa was more likely with topical administration of B-VEC than with placebo. Pruritus and mild systemic side effects were observed in patients treated with B-VEC. Longer and larger trials are warranted to determine the durability and side effects of B-VEC for this disease. (Funded by Krystal Biotech; GEM-3 ClinicalTrials.gov number, NCT04491604.).Copyright © 2022 Massachusetts Medical Society.

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