How does B-VEC work?
COL7 keeps the skin’s upper layer, the epidermis, attached to its lower layer, the dermis. A lack of COL7 causes the epidermis to separate from the dermis, causing severe blistering.
B-VEC delivers a healthy or working copy of the human COL7A1 gene directly to a patient’s skin cells, using a modified virus as a carrier. The working gene copy allows cells to produce the COL7 protein, helping wounds to close and preventing skin blistering.
B-VEC in clinical trials
B-VEC was investigated in a randomized Phase 1/2 clinical trial, called GEM-1 (NCT03536143), in people with recessive dystrophic epidermolysis bullosa (RDEB).
The Phase 1 portion of the study recruited two adults, and treated two wounds in each patient with topical B-VEC or a placebo.
Its Phase 2 portion would involve four adults (ages 19 to 33) and two children (ages 14 and 15) with severe generalized RDEB. Wounds covered an area of up to 20 square centimeters (cm2) in two adults and the children, and 10 cm2 for the two other adults. In total, 10 wounds were treated with BVEC, seven of which were recurring and three chronic, with a matched wound given a topical placebo. Recurring wounds were those that were open for less than 12 weeks (about three months) but opened and closed spontaneously, while chronic wounds had been open for more than 12 weeks.
The wounds were treated daily for the first five days, and then at days 30, 60, and 90 until wound closing. Treatment efficacy and safety were analyzed through monthly imaging and biopsies.
Trial results, announced in October 2019, found nine of the 10 wounds (90%) closed fully with BVEC’s use, in an average of 17.4 days. Moreover, as of the last measured time point, the wounds stayed closed over 113 days (almost four months). The chronic wound that failed to fully heal at 90 days (42% closure) had been open for four years, researchers reported, and required repeat treatment to completely close within seven days, which lasted for more than 100 days.
Treatment in both trial phases was considered safe and well-tolerated, with no inflammation nor irritation after B-VEC dosing.
A pivotal Phase 3 trial called GEM-3 (NCT04491604) opened in the U.S. in 2020 and enrolled 31 people, a mix of children and adults ranging in age from 1 to 44, with DEB. This study is evaluating B-VEC against a topical placebo on one or more wound pairs in these patients — under 20 cm2, 20 to 40 cm2, and 40 to 60 cm2 — with pairs selected by a site trial investigator. B-VEC is being applied to each treated wound at 400 million plaque forming units (PFU, a measure of viral particles) for smaller wounds and 1,200 million PFU/wound for larger ones.
Most (61%) of the enrolled patients are age 18 or younger, and fewer than 10% have dominant DEB (a single disease-causing COL7A1 mutation).
Treatment is being given weekly in this six-month study, and continuing until investigators determine that a wound has completely closed, the trial’s primary goal at 24 weeks (nearly six months). Secondary goals include complete healing at 12 weeks, a mean change in pain severity by 24 weeks (nearly one year), and the proportion of B-VEC versus placebo wounds showing at least 75% healing at 24 weeks. Safety also will be evaluated throughout.
In preparation for the GEM-3 trial, Krystal opened an observational, non-treatment study (NCT04214002) of the natural history of wounds in DEB. This four-month study at Stanford University, in California, involved about 20 patients.
The U.S. Food and Drug Administration designated B-VEC an orphan drug in November 2017, and as a regenerative medicine advanced therapy in June 2019. The European Medicines Agency designated the topical gene therapy a priority medicine in 2019.
All of these designations are designed to speed and support the process of testing and reviewing investigational treatments.
Krystal Biotech opened a second gene therapy facility, called Astra, in the Pittsburgh area of Pennsylvania in early 2020. That site is set to produce B-VEC and other gene therapy treatments for testing and commercial use, should they be approved.
Last updated: April 19, 2021
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