Krystal Seeks Approval for Dystrophic Epidermolysis Bullosa Gene Therapy
B-VEC recently showed efficacy in the phase 3 GEM-3 trial.
Krystal Biotech has submitted a biologics license application (BLA) for B-VEC (beremagene geperpavec), its gene therapy for the potential treatment of dystrophic epidermolysis bullosa (DEB).1
The BLA submission is based off positive data from the phase 1/2 GEM-1/2 study (NCT03536143) and the phase 3 GEM-3 study (NCT04491604). Positive data from the GEM-3 study were recently 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.2
“The unmet medical need for DEB patients remains very high and our relentless pursuit of a treatment for this disease continues with the same sense of urgency that we have always had since the founding of Krystal Biotech,” Suma Krishnan, president, research & development, Krystal, said in a statement.1 “We look forward to working with the FDA in its review of our BLA submission.”
B-VEC is a topical, re-dosable gene therapy. It is directly applied to DEB wounds and delivers 2 copies of the COL7A1 gene directly to the skin to make functional COL7 protein. Krystal plans to submit a marketing authorization application with the EMA in the second half of 2022.
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The GEM-1/2 trial was a single-center, randomized, intra-patient placebo-controlled, open-label trial that enrolled 9 patients with dystrophic epidermolysis bullosa patients evaluated over 12 weeks. The trial met both its mechanistic and clinical endpoints and investigators found that B-VEC was well-tolerated with no serious treatment-related adverse events (AEs).
Recently in the GEM-3 study, 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).2 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).
Pain and patient-reported outcome data were also positive, with a significant change from baseline in pain response at week 22 (P = .02), and near-significant changes at weeks 24 (P = .07) and 26 (P = .06). There was also 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. Safety findings were similar between GEM-1/2 and GEM-3, and the therapy continues to be well-tolerated.
“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.
