Vyjuvek in Japanese DEB patients shows efficacy similar to US studies
Topical gene therapy under review in Japan, with decision expected soon
In a small study in Japan, the topical gene therapy Vyjuvek (beremagene geperpavec) was shown to work similarly to what was seen in an earlier U.S.-based trial, now safely and durably closing wounds for four Japanese people with dystrophic epidermolysis bullosa (DEB).
The new data comes from an open-label extension (OLE) study involving patients in the Asian nation with the rare disease, which is marked by very fragile skin.
The data are consistent with observations from previous studies that supported Vyjuvek’s U.S. approval for DEB in 2023. The gene therapy was also approved in the European Union earlier this year, for use in DEB patients from birth.
It’s now under regulatory review in Japan, with a decision due later this year. This study had sought to further establish Vyjuvek’s safety and effectiveness among Japanese DEB patients.
“The results of the Japan OLE study are in agreement with the U.S. … studies, demonstrating the efficacy and safety of [Vyjuvek] in Japanese patients with DEB,” the researchers wrote.
Titled “Efficacy and Safety of the Topical Gene Therapy Beremagene Geperpavec-svdt (B-VEC) in an Open-Label Study of Japanese Subjects With Dystrophic Epidermolysis Bullosa,” the study was published in The Journal of Dermatology. Of the study’s 13 authors, nine are affiliated with Krystal Biotech, Vyjuvek’s developer.
People with DEB have mutations in the COL7A1 gene that result in a lack of collagen 7 (COL7), a structural protein that helps hold skin layers together. This leaves patients with fragile skin that easily blisters and tears, driving the formation of open wounds that heal slowly.
Vyjuvek, formerly known as B-VEC, is designed to resolve skin wounds for people with DEB by delivering healthy copies of COL7A1 directly to skin cells, enabling them to make their own COL7 protein. It is applied as a gel directly onto open wounds once weekly.
Vyjuvek closed wounds in 4 Japanese patients in 3 months
In the U.S.-based Phase 3 GEM-3 trial (NCT04491604), Vyjuvek improved wound healing relative to a placebo among more than 30 DEB patients. In a subsequent OLE study (NCT04917874), also conducted in the U.S., the gene therapy was associated with continued wound closure, good tolerability, and high patient satisfaction.
The OLE study (jRCT2053230075) described in this report was launched in 2023 to further establish Vyjuvek’s safety and efficacy among Japanese individuals with DEB.
“The present study was designed to extend the efficacy and safety of [Vyjuvek] in a cohort of Japanese DEB patients, confirming that no noteworthy differences in treatment response arise from varying ethnic backgrounds,” the researchers wrote.
It enrolled five people with recessive DEB, ranging in age from 12.8 to 68.6. The participants were expected to receive weekly Vyjuvek applications for up to a year. A designated primary wound was the main focus of treatment, but any leftover gene therapy could be applied to secondary wounds during the study.
The present study was designed to extend the efficacy and safety of [Vyjuvek] in a cohort of Japanese DEB patients, confirming that no noteworthy differences in treatment response arise from varying ethnic backgrounds.
One person withdrew from the study after eight weeks due to challenges following wound dressing disposal guidelines, leaving four participants who could be evaluated for wound closure.
The study’s main goal was to evaluate primary wound closure after six months, which was considered achieved if an investigator deemed the wound closed at week 22, 24, or 26 — overall, a time period spanning five to six months.
This goal was met with all four patients. All wounds were also completely closed at the three-month mark (week eight, 10, or 12), meeting a secondary efficacy goal.
Results of this study ‘consistent’ with those seen in US trial
In the U.S.-based studies, complete wound closure was defined as researchers determining wounds to be closed at two consecutive assessments, spaced two weeks apart.
When defined in this same way, all four participants in the new study still met that threshold, “demonstrating comparability between the Japan OLE and Phase 3 studies for wound healing,” the investigators wrote.
These same wounds were further assessed after nine months and one year as exploratory indicators of the durability of response. Durable complete closure was observed at these timepoints for three of the four participants.
All reported side effects were mild or moderate in severity, and none were considered related to Vyjuvek treatment by the investigators. None of the evaluable participants developed antibodies against COL7.
“Overall, these [adverse events] resembled those reported during the Phase 3 and U.S. OLE studies and were consistent with common symptoms in the DEB patient population,” the researchers wrote.
Patient-reported outcome measures generally suggested reduced wound pain during dressing changes, improvements in skin-specific life quality, and maintenance of moderate-to-high treatment satisfaction, per the study.
The researchers noted that the small number of participants limits interpretation of these measures. But the findings were generally similar to previous studies, the team noted.
Altogether, “the results of this study are consistent with the results of the U.S. Phase 3 and OLE studies of [Vyjuvek], indicating no apparent difference in efficacy or safety for Japanese [patients],” the researchers wrote.
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