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B-VEC Gene Therapy Heals Recessive Dystrophic Epidermolysis Bullosa Wounds

Positive interim results from a phase 3 study presented at AAD 2022 bolster recently published phase 2 data.

Beremagene geperpavec (B-VEC, Krystal Biotech) promotes durable wound healing in patients with recessive dystrophic epidermolysis bullosa (RDEB), according to preliminary data from the phase 3 GEM-3 trial (NCT04491604).1

Data from the trial were presented at the American Academy of Dermatology (AAD) 2022 Annual Meeting, March 25-29, Boston, Massachusetts, by principal investigator M. Peter Marinkovich, MD, associate professor, department of dermatology, Stanford University.

“It’s the very first topical gene replacement therapy in dermatology... We've seen success in the phase 3 trial and it may be the case that more dermatologists will be seeing these patients come in since the therapy is so easy to do,” Marinkovich said in an interview with our sister site, HCPLive. 

Marinkovich and investigators found that a significantly greater proportion of wounds treated with B-VEC exhibited complete wound healing compared with placebo at 3 months (absolute difference, 50.3% [95% CI, 28.7-72.0]; P <.005) and 6 months (absolute difference, 45.8% [95% CI, 23.6-68.0%]; P <.005). One patient with dominant DEB had their B-VEC treated wound meet the endpoint of complete wound healing at 6 months while their placebo-treated wound did not meet this endpoint. At 6 months, 15 of 17 discordant wound pairs showed response to B-VEC but not placebo.

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Almost half (49.7%) of wounds treated with B-VEC were completely healed at both 3 and 6 months compared with 7.1% of wounds treated with placebo, demonstrating durability of response. Most wounds (66.7%; n = 14) closed at 3 months were also closed at 6 months, compared with 33.3% of placebo-treated wounds meeting the same endpoint (P = .02).

Investigators also found improvements in pain and patient-reported outcomes in wounds treated with B-VEC consistent with wound healing. They observed a significant change from baseline in pain response at week 22 (P = .02), with near-significant changes at weeks 24 (P = .07) and 26 (P = .06) as well as a trend toward decreased pain in B-VEC versus placebo treated wounds. Improvements from baseline were also seen in patient-reported outcome measures such as EQ-5D-5L and Skindex-29.

“We have only been able to offer supportive therapy for these patients...we just watch the wounds happen and provide wound care, but are not able to reverse the disease... this is an opportunity to do that. This therapy actually corrects the molecular defect in the skin, promotes wound healing and more importantly promotes durability of wound healing in the skin,” Marinkovich told HCPLive. “This has already impacted patients in the trial and we’re in the open-label phase of the trial right now...the patients benefit by seeing wound healing, they have a decrease in pain, and decrease in discomfort, and it’s really made a positive impact on their lives.”

B-VEC was generally well-tolerated with no treatment-related discontinuations. Most adverse events (AEs) were mild; 1 of these, mild erythema, was considered to bepossibly related to treatment. There were 5 reported serious AEs: cellulitis, anemia (n = 2), diarrhea, and positive blood culture. None of these were determined to be related to treatment.

Following the success of the GEM-3 study, in which the primary and secondary outcomes were met, patients treated with B-VEC have the option to enroll in an ongoing open-label, long-term extension study (NCT04917874). Data from the phase 1/2 GEM 1/2 trial (NCT03536143) of B-VEC were also recently published in Nature Medicine that reinforce the positive data presented from GEM-3 at the AAD 2022 meeting.2

1. Marinkovich MP, Gonzalez ME, Guide S, et al. GEM-3: A phase 3 study of beremagenegeperpavec (B-VEC), an investigational, topical gene therapy, for the treatment of dystrophic epidermolysis bullosa (DEB). Presented at: AAD 2022 Annual Meeting, March 25-29, Boston, Massachusetts.
2. Gurevich I, Agarwal P, Zhang P, et al. In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial. Nat Med. Published online March 28, 2022. doi: 10.1038/s41591-022-01737-y