A Phase 3 trial testing the world's first topical gene therapy has reported extraordinary results in children suffering from a rare blistering skin disease. The gene therapy gel was seen to completely heal wounds that had been open for years.
Dystrophic epidermolysis bullosa (DEB) is a rare skin disease that results in skin constantly blistering, and often leaves open wounds that are unable to heal. The condition is caused by a mutation in the COL7A1 gene that renders a person unable to produce a key collagen protein.
The new therapy is a gel designed to deliver working copies of the COL7A1 gene directly to wound tissue. This, in theory, should trigger the production of key collagen proteins needed for the skin to heal. The functional genes are delivered via a modified herpes virus that is unable to replicate and spread to other parts of the body but is able to evade the body's immune defenses.
Reporting in The New England Journal of Medicine, the results of a Phase 3 double-blind, placebo-controlled trial are nothing short of spectacular. Patients were treated with the gene therapy gel weekly, and after three months 71% of those receiving the active gel were completely healed. By six months 67% of wounds treated in the trial were still healed.
One participant in the trial, a 22-year-old named Vincenzo Mascoli, had been suffering from open wounds for his entire life, but within months of using the gene therapy gel his wounds had healed.
“After four months, I saw an improvement on a large wound on my back that I had for 20 years,” said Mascoli. “After six months, the wound had healed completely and was much less painful.”
Unfortunately, because the effects of the gel are not permanent, many patients have seen some of their wounds return in the months after the trial finished. The researchers suggest this is to be expected, but considering there were no adverse effects seen with repeated administration of the gel it is possible ongoing treatments could be effective over long periods of time.
Pharma company Krystal Biotech is already working closely with the US Food and Drug Administration (FDA) for market approval. A decision is expected sometime in the first quarter of 2023.
While DEB is a rare disease, this specific topical gene therapy is likely to be the first of many applications for the novel technology. There are a number of other epidermolysis bullosa skin disorders caused by single gene mutations that hypothetically could be treated by this technology.
In its current form, the gene therapy cannot penetrate intact skin. So it can only treat pre-existing wounds, not prevent them from breaking down in the first place. Future iterations of the technology will explore different delivery modes that could target a variety of different skin diseases.
The new study was published in The New England Journal of Medicine.
Source: Stanford Medicine
