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.