Gene Therapy B-VEC Is Safe, Leads to Sustained Wound Healing in RDEB Patients, Phase 1/2 Trial Shows

Gene Therapy B-VEC Is Safe, Leads to Sustained Wound Healing in RDEB Patients, Phase 1/2 Trial Shows

Topical treatment with B-VEC, formerly known as KB103, is safe and leads to complete and durable wound healing in people with recessive dystrophic epidermolysis bullosa (RDEB), final results from a small Phase 1/2 trial suggest.

RDEB is caused by mutations in the COL7A1 gene. This leads to a defective collagen VII (COL7) protein, which in turn results in separation of the epidermis from the dermis (two skin layers), and blisters.

Krystal Biotech’s B-VEC (bercolagene telserpavec) is a gene therapy designed to deliver functional COL7A1 directly to skin cells by using a modified, harmless herpes simplex virus.

In the GEM-1 trial (NCT03536143), Phase 1 included two adults with severe generalized RDEB, who received either topical B-VEC or a placebo. Each patient had two wounds that were approximately 10 cm2 (10 square centimeters) in area.

In turn, Phase 2 included two adults ages 22 and 19, and two pediatric patients, ages 14 and 15, all with severe generalized RDEB. From each patient, three wounds up to 20 cm2  were selected to receive either B-VEC or placebo. Researchers noted that the 19-year-old patient voluntarily discontinued participation after 30 days due to inability to travel to the clinical site.

Among the six wounds treated with B-VEC and included in the final analysis, two were categorized as chronic, or open for longer than 12 weeks, and four were recurring — less than 12 weeks, open and close spontaneously.

Two more patients ages 21 and 33, also with severe generalized RDEB, were later enrolled in the Phase 2 part. Two wounds were selected from each participant to also receive either B-VEC or placebo.

Overall, 10 wounds were treated with B-VEC, seven of which were recurring and three chronic.

Patients received B-VEC every other day for two weeks, or until the wound closed completely. Monthly follow-ups included biopsies, as well as imaging and safety assessments.

In line with a prior update, the results indicated that B-VEC was well-tolerated in all patients following repeated dosing, with no inflammation or irritation.

Regarding efficacy, nine wounds (90%) closed completely after treatment with B-VEC. The average time to complete closure was 17.4 days. As assessed at the last timepoint, wounds were still closed after an average of 113 days.

A chronic wound reportedly open for four years had not healed fully at day 90 after treatment with B-VEC (42% closure), the results showed. Repeat treatment led to complete closure within seven days, which lasted for more than 100 days.

In the two patients who enrolled later, researchers found a correlation between molecular correction and wound healing. Imaging analyses revealed production of functional COL7 and anchoring fibrils — large structures that hold the skin together — in treated wounds.

The two wounds of these two patients that were treated with B-VEC closed completely within eight days, remaining closed for at least 114.5 days.

“We are encouraged by the results to date and believe that B-VEC has the potential to be a very convenient and elegant approach to treating recurring and chronic wounds for patients suffering from DEB,” Suma Krishnan, founder and chief operating officer at Krystal Biotech, said in a press release.

Given these positive results and pending clearance from the U.S. Food and Drug Administration (FDA), the company now plans to start a pivotal trial of B-VEC, intended to provide evidence for regulatory approval.

Earlier this year, B-VEC received priority designation in Europe and regenerative medicine advanced therapy (RMAT) from the FDA for the treatment of DEB.

Iqra holds a MSc in Cellular and Molecular Medicine from the University of Ottawa in Ottawa, Canada. She also holds a BSc in Life Sciences from Queen’s University in Kingston, Canada. Currently, she is completing a PhD in Laboratory Medicine and Pathobiology from the University of Toronto in Toronto, Canada. Her research has ranged from across various disease areas including Alzheimer’s disease, myelodysplastic syndrome, bleeding disorders and rare pediatric brain tumors.
Total Posts: 22
José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
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Iqra holds a MSc in Cellular and Molecular Medicine from the University of Ottawa in Ottawa, Canada. She also holds a BSc in Life Sciences from Queen’s University in Kingston, Canada. Currently, she is completing a PhD in Laboratory Medicine and Pathobiology from the University of Toronto in Toronto, Canada. Her research has ranged from across various disease areas including Alzheimer’s disease, myelodysplastic syndrome, bleeding disorders and rare pediatric brain tumors.
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