Vyjuvek, Topical Gene Therapy, Aids Wound Healing in DEB Trial
Treatment with Vyjuvek (previously called B-VEC) — a topical gene therapy for dystrophic epidermolysis bullosa (DEB) — improved wound healing with good tolerability over six months, according to top-line results of the Phase 3 GEM-3 trial.
“We are thrilled to announce positive results from our pivotal GEM-3 trial of VYJUVEK which showed that this topical gene therapy led to durable wound healing in dystrophic EB wounds,” Suma Krishnan, founder and chief operating officer of Krystal Biotech, Vyjuvek’s developer, said in a press release.
Krystal plans on submitting a Biologics License Application — a request to introduce a biologic product into commercial use — to the U.S. Food and Drug Administration in the first half of 2022. A similar application in Europe is planned shortly after.
“With these results in hand, we look forward to advancing discussions with regulatory authorities and will work quickly to bring this potential first-ever treatment to patients with dystrophic EB and their families who are in desperate need,” Krishnan added.
DEB is a rare disease in which the skin is fragile due to mutations in the COL7A1 gene, which codes for a portion of type VII collagen (COL7) — a protein that helps hold skin layers together.
Vyjuvek is a topical and re-dosable gene therapy. It works by delivering healthy copies of the COL7A1 gene directly to wounds, using a modified virus as a carrier. The working gene allows skin cells to produce functional COL7, helping wounds to heal and preventing skin blistering.
The GEM-3 trial (NCT04491604) compared healing in 31 patients with DEB, ages 1 to 44 — each person with a pair of wounds. One of the wounds was treated weekly with Vyjuvek (then B-VEC) and the other weekly with a placebo, both until the wounds closed. If wounds reopened, Vyjuvek treatment would be resumed.
Results at six months showed that 67% of Vyjuvek-treated wounds had completely healed, as compared with 22% of the wounds treated with a placebo. This was the trial’s primary goal.
At three months, 71% of the wounds treated with Vyjuvek achieved the secondary goal of complete healing, as compared with 20% of the wounds given the placebo.
Vyjuvek was superior to the placebo to a statistically significant degree in completely closing wounds at both three and six months, a further analysis revealed.
The therapy was well-tolerated over the six months, with no serious treatment-related adverse events reported, and no treatment discontinuations. One mild Vyjuvek-related adverse event was reported during the trial; the release did not provide details.
As for whether Vyjuvek prompts an immune response, the data were consistent with a Phase 1/2 study that found no meaningful change in the levels of antibodies against COL7 or HSV-1 (the therapy’s carrier).
“Today’s positive B-VEC results represent the culmination of years of study on the molecular basis and genetic correction of this disease,” said Peter Marinkovich, MD, a dermatology professor at Stanford University, one of the trial sites. “Finally, dystrophic EB patients may have an easily administered genetically targeted therapy which has been shown to promote durable wound healing in this clinical trial.
“This is a long overdue milestone for patients living with this disease, and one that has potential to drastically change the treatment paradigm,” Marinkovich added.
To support a potential global launch of Vyjuvek, Krystal is constructing a second manufacturing facility, Astra, which is expected to open in 2022.
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. Participants in GEM-3 had the option to join this trial, which may also include patients who met the inclusion criteria of the Phase 3 trial but were unable to participate. More information on enrollment, contacts, and locations can be found here.