Half of wounds treated with the gene therapy had complete healing at both months 3 and 6 compared to 7% of placebo-treated wounds.
The full data readout from the phase 3 GEM-3 study (NCT04491604) of beremagene geperpavec (B-VEC; Krystal Biotech) further support the gene therapy’s ability to promote wound healing and reduce pain in patients with dystrophic epidermolysis bullosa (DEB).1
Investigators in the trial found that 67% of wounds treated with B-VEC had complete healing at 6 months compared to 22% not treated with B-VEC in 31 patients (difference, 46%; 95% CI [24-68]; P=.002). At 3 months, 71% of wounds treated with B-VEC were completely healed compared to 20% exposed to placebo (difference, 51%; 95% CI [29-73]; P <.001). Pain severity during wound-dressing decreased by .88 from baseline to week 22 in B-VEC-treated wounds and by .71 in placebo-treated wounds (adjusted least-squares mean difference, −0.61; 95% CI [−1.10 to −0.13]) with similar changes at weeks 24 and 26. The therapy was well-tolerated, with common adverse events (AEs) including pruritis and chills.
“The impressive phase 3 results with B-VEC are the best we have seen to date in patients with DEB and, if approved, B-VEC provides hope for these patients suffering through debilitating and potentially life-threatening symptoms associated with the disease,” first author and primary investigator Peter Marinkovich, MD, director, Blistering Disease Clinic, Stanford Health Care, and Associate Professor of Dermatology, Stanford University School of Medicine, said in a statement.2
Results from the GEM-3 trial, topline data from which were presented in at the American Academy of Dermatology (AAD) 2022 Annual Meeting in March 2022, supported Krystal’s submission of a biologics license application for B-VEC in June 2022.3,4The FDA accepted the BLA for priority review in August 2022 with a PDUFA action date of February 17, 2023.5
The double-blind, intra-patient randomized, placebo-controlled GEM-3 trial assessed B-VEC in wounds on patients at least 6 months of age with genetically confirmed DEB.1 Investigators selected a primary wound pair on each patient matched in size, region, and appearance, and wounds within each pair were randomized to receive weekly applications of placebo or B-VEC for 26 weeks. The study’s primary end point was complete wound healing in treated versus untreated wounds at 6 months. Secondary endpoints included complete wound healing at 3 months and changes from baseline in pain severity during wound dressing at weeks 22, 24, and 26 assessed by a visual analogue scale with scores ranging from 1-10.
Study participants had a mean age of 16 years (range, 1-44) and over half (61%) were 18 years old or younger. All but 1 participant, who had a dominant form of DEB, had recessive DEB. Wounds were of similar size, with a median area of 10.6 cm2 in treated wounds and 10.4 cm2 in placebo wounds. Wound sizes ranged from 2.3 cm2 to 57.3 cm2 in the 31 participants.
Investigators also assessed improvements in the EQ-5D-5L quality-of-life questionnaire dimensions at 6 months as compared with baseline and found that most participants improved by at least 1 health level or had no change; similarly, Skindex-29 scores were similar between baseline and follow-up. Durability analyses revealed that a higher percentage of wounds treated with B-VEC had complete closure across more time points than placebo wounds and 50% of these wounds had complete healing at both months 3 and 6 compared to 7% of placebo wounds (43% difference; 95% CI [23-63]). Subgroup analyses across sex, age, and wound size did not reveal significant differences, perhaps due to too-small subgroups.
B-VEC was generally well-tolerated, with 18 participants (58%) having at least 1 AE, the majority of which were mild or moderate. Five serious AEs included diarrhea, anemia, cellulitis, and a positive blood culture related to a hemodialysis catheter, but none were considered related to B-VEC. One AE of mild erythema was considered related to B-VEC treatment. Squamous-cell carcinoma of the skin, at wound sites not exposed to B-VEC or placebo, occurred in 3 participants (10%).
“B-VEC was developed by Krystal scientists as a potential first-in-class therapy for DEB,” Suma Krishnan, president, research & development, Krystal Biotech, said in a statement.2 “We are working closely with the FDA to get B-VEC approved and deliver a meaningful benefit to patients with this debilitating disease.”