M. Peter Marinkovich, MD, and Alfonso L. Sabater, MD, PhD, offered their respective perspectives on the recent FDA approval of the topical and redosable gene therapy for DEB.
After many years without much in terms of therapeutic options, patients with dystrophic epidermolysis bullosa (DEB) were given a new option for treatment with the FDA’s decision to approve Krystal Biotech’s beremagene geperpavec (Vyjuvek), also known as B-VEC, a topical and redosable gene therapy.1 The gene therapy, the first for this patient population, is indicated for patients 6 months or older.
B-VEC’s biologics license application (BLA) was supported by data from 2 intrapatient, placebo-controlled clinical trials: the phase 2 GEM-1/2 (NCT03536143) study and the phase 3 GEM-3 study (NCT04491604).2,3 GEM-3 data showed that in addition to being well-tolerated, in 31 patients, 67% of wounds treated with B-VEC had complete healing at 6 months compared with 22% of those not treated with B-VEC (difference, 46%; 95% CI, 24-68; P = .002). All told, In the published findings from the GEM-3 trial, 71% of wounds treated with B-VEC were completely healed at 3 months compared with 20% of those exposed to placebo (difference, 51%; 95% CI, 29-73; P <.001). Additionally, pain severity during wound-dressing reportedly decreased by 0.88 points from baseline to week 22 in B-VEC-treated wounds, compared with a decrease of 0.71 in placebo-treated wounds, (adjusted least-squares mean difference, −0.61; 95% CI, −1.10 to −0.13) with similar changes reported at week 24 and week 26.
In reaction to the agency’s approval, CGTLive™ connected with a pair of investigators from the clinical development of B-VEC to find out more about how this new option might impact clinical care, and to find out their immediate reactions. The first of those inquired with was M. Peter Marinkovich, MD, a primary investigator in the GEM-3 study and an associate professor of dermatology, faculty member of the Program in Epithelial Biology and the Stanford Cancer Biology Program, as well as director of the Stanford Bullous Disease and Psoriasis Clinics at Stanford University.
The second was Alfonso L. Sabater, MD, PhD, an associate professor of clinical ophthalmology, the medical director of the Ocular Surface Program, and the director of the Corneal Innovation Lab at the Bascom Palmer Eye Institute of University of Miami Miller School of Medicine, who has been involved in a compassionate use program for the therapy treat the ocular complications of a patient with DEB in a compassionate use program. The patient, who presented with cicatrizing conjunctivitis, received surgical symblepharon lysis with pannus removal in the right eye. In addition to routine post-surgical management, the patient's right eye was treated with B-VEC at regular intervals after surgery.4
Peter Marinkovich, MD: I’m so happy for the patients that they now have an approved corrective therapy in their home.
Alfonso L. Sabater, MD, PhD: I’m extremely happy for all the patients with dystrophic epidermolysis bullosa. This is a devastating disease, and it’s great that these patients will finally have an effective treatment for their skin lesions.
Peter Marinkovich, MD: I think many more local primary care pediatricians and dermatologists will start to treat epidermolysis bullosa patients now that they have an easy corrective therapy they can prescribe. This will be a benefit for epidermolysis bullosa patients as well.
Alfonso L. Sabater, MD, PhD: This is the first-ever redosable gene therapy, which opens the door to future gene therapies for other conditions. I’m a cornea specialist, and unfortunately, B-VEC is not approved yet for ocular treatment. However, I’m sure dermatologists and other physicians who treat the skin manifestations of this condition must be excited to have an effective treatment for their patients.
Peter Marinkovich, MD: It’s especially important to start treating at a young age, in order to help prevent chronic wounding and fibrosis issues.
Alfonso L. Sabater, MD, PhD: Beremagene geperpavec is a topical investigational herpes simplex virus type 1–based gene therapy designed to restore collagen VII (or C7) protein by delivering COL7A1. In the clinical trials, B-VEC enhanced the healing of skin lesions and reduced pain (compared to placebo) during wound-dressing changes.