How does Vyjuvek 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.
Vyjuvek 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.
Vyjuvek in clinical trials
Vyjuvek was investigated in a randomized Phase 1/2 clinical trial, called GEM-1 (NCT03536143), in people with recessive dystrophic epidermolysis bullosa (RDEB). The therapy is referred to as B-VEC in most studies.
This trial evaluated Vyjuvek’s safety and effectiveness in six adults (five men and one woman) and three children (two boys and one girl) with RDEB. Matched wounds in each patient were treated with either Vyjuvek or a placebo gel, most commonly every two to three days to correspond with bandage changes, for 12 weeks (about three months).
Results showed that all Vyjuvek-treated wounds closed and remained healed for at least three months, with the exception of a chronic, five-year-old wound on a foot. This wound partly closed within one month of treatment, was completely resolved upon re-treatment and remained closed throughout eight months of monitoring.
In contrast, the wounds treated with the placebo gel healed and re-blistered at variable rates throughout the trial.
Two lateral four-year-old wounds on the chest of a 10-year-old boy that were treated with two, 25-day cycles of either Vyjuvek or a placebo gel showed Vyjuvek-treated wound reduced by 70%, while that given the placebo gel showed only a 34% reduction.
A study updating trial findings, published in March 2022, reported that resolved wounds remained closed for at least three months and up to eight months.
A pivotal Phase 3 trial called GEM-3 (NCT04491604) enrolled 31 people in the U.S., a mix of children and adults ranging in age from 1 to 44, with DEB. It evaluated Vyjuvek 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. Vyjuvek was 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 were age 18 or younger, and fewer than 10% have dominant DEB (a single disease-causing COL7A1 mutation). A total of 29 people completed the six-month study and its safety follow-up visit, which was scheduled 30 days after the last treatment.
Top-line GEM-3 results showed that Vyjuvek’s use improved wound healing with good tolerability over six months, with 67% of treated wounds completely healed at six months, as compared with 22% of the wounds given a placebo gel, and meeting the study’s primary goal.
Vyjuvek was also seen superior to the placebo to a statistically significant degree in completely closing wounds at both three and six months.
The therapy was well-tolerated over the six months, with no serious treatment-related adverse events reported, and no treatment discontinuations.
An open-label extension study (NCT04917874) is underway to test the gene therapy over about a year and a half in patients 6 months or older. GEM-3 participants had the option to join this trial, due to conclude in December 2022.
Based on GEM-3 and earlier trial findings, Krystal announced plans to submit a Biologics License Application — a request to introduce a biologic product into commercial use — to the U.S. Food and Drug Administration. A similar application to European regulators is expected to follow.
Krystal had also opened an observational, four-month and non-treatment study (NCT04214002) of the natural history of wounds in DEB at Stanford University, in California, that was to involve about 20 patients. This study was terminated due to restrictions necessitated by the COVID-19 pandemic.
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 Vyjuvek and other gene therapy treatments for testing and commercial use, should they be approved.
Last updated: April 01, 2022
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