A first-of-its-kind topical gene therapy developed by Krystal Biotech, Inc. in collaboration with Alfonso Sabater, MD, PhD, from the Bascom Palmer Eye Institute in Miami, Florida, restored the vision of a 14-year-old patient with dystrophic epidermolysis bullosa (DEB).
Give me a quick refresh on Krystal Biotech.
Based in Pittsburgh, Pennsylvania, the biotechnology company is developing redoable gene therapies for treating patients with debilitating diseases; its proprietary gene delivery platform enables off-the-shelf treatments for serious diseases.
Tell me more about this platform.
The Skin TARgeted Delivery (STAR-D) platform contains an engineered viral vector that is derived from the herpes simplex virus type 1 (HSV-1) optimized for both local and repeat gene transfer to epithelial cells.
Now DEB.
DEB is a rare genetic condition caused by mutations in the COL7A1 gene that encodes for collagen VII. A deficiency in collagen VII leads to the skin and mucous membranes being so fragile that any friction or minor injury results in painful blisters.
In severe forms of the disease, it can also lead to blistering, erosion, and scarring of the cornea.
And this patient case?
Legally blind for most of his life due to his condition, the patient underwent two surgeries on his left eye to remove the scar tissue that clouded his vision.
Although these surgeries were initially successful and partially restored his vision, the blisters and subsequent scarring persisted, causing his eyesight to worsen again.
How about the topical gene therapy?
Krystal Biotech’s Vyjuvek (beremagene geperpavec-svdt), a topical gene therapy administered to active blisters via gel, was just approved by the FDA in May 2023.
The gel, a herpes-simplex virus type 1 (HSV-1) vector-based gene therapy, is indicated for the treatment of wounds in patients ages 6 months+ with DEB.
How does it work?
The therapy delivers working copies of the COL7A1 gene using an inactivated herpes simplex virus to prevent new blisters while the skin heals.
To note, the gel must be reapplied, as it does not permanently change the DNA of the cells.
I thought this was an eye drop … ?
It is (now, at least).
Before being approved by the FDA, the patient enrolled in a clinical trial for Vyjuvek and experienced an improvement in the blisters on his skin. As such, Dr. Sabater hypothesized that this treatment could be adapted to address the blisters on the patient’s eyes.
In collaboration with Krystal Biotech, the treatment was reformulated to function as an eye drop by removing the gel-like ingredient from its formula.
Did it go through any clinical trials?
While the gel version of Vyjuvek underwent one randomized clinical trial (see page 14 of its prescribing information), the new formula as a drop was tested on mice.
Following 2 years of testing for safety and efficacy, the FDA granted compassionate use approval for the patient to try the eye drop formulation of Vyjuvek.
Refresh: Compassionate use (also called “single patient investigational new drug [IND]”) allows for the use of a non-FDA-approved drug to diagnose, monitor or treat a patient or patients rather than obtain information that is normally collected in clinical trials.
When did they start this novel treatment?
In August 2022, Dr. Sabater operated on the patient’s right eye to remove the remaining scar tissue causing severe vision loss.
Immediately following the surgery, the gene therapy eye drop was instilled once a month, and steadily over time, the vision in the right eye has improved to 20/25, where it has since remained stable.
Go on…
Following the success of the treatment on the right eye, Dr. Sabater operated on the patient’s left eye in March 2023; the topical treatment was then started.
To note, the left eye has shown similar improvement and is nearing 20/50 vision.
Next steps?
Dr. Sabater and Krystal Biotech are working to organize a future clinical trial that would enroll additional patients to receive the same therapy as this recent patient case.
Further, these gene therapy eye drops could potentially treat other diseases, such as Fuchs’ endothelial corneal dystrophy, by switching the gene delivered by the virus.