Krystal Biotech, Inc., a clinical-stage biopharmaceutical company focused on gene therapies for dermatological diseases, recently announced positive results from a Phase 3 clinical trial on its investigational compound Beremagene Geperpavec (B-VEC), a topical gene therapy designed to treat the debilitating skin condition dystrophic epidermolysis bullosa (DEB).
DEB is the most serious manifestation of epidermolysis bullosa, an ultra-rare disease caused by a faulty gene that makes one’s skin fragile and blister easily. Patients with DEB experience extensive skin erosions in response to minor injuries or frictions, such as rubbing or scratching.
At its root, the missing or mutated gene in DEP patients disrupts the normal functioning of Collagen VII (COL7), a protein that plays a crucial role in adhesion of epidermis to the dermis.
Krystal’s Phase 3 randomized, double-blind, intra-patient placebo-controlled study evaluated the efficacy and safety of B-VEC as a redosable gene therapy in DEB patients aged 6 months and older. The goal was to deliver COL7A1 gene to skin cells locally and induce expression of the full-length normal COL7 protein to correct the underlying molecular defect.
Participants were treated weekly with the topical B-VEC therapy.
“In this first-ever clinical trial of a redosable topical gene therapy, we are pleased to see that these data show the potential of B-VEC to address the underlying cause of the disease and delineate B-VEC as an easily administered, well tolerated therapy,” Suma Krishnan, President of Research and Development at Krystal Biotech, Inc., said in a press release.
“For so many years, all we have been able to offer DEB patients was palliative care, so it is now gratifying to have a potential corrective treatment option for this deserving group of patients,” she added. “We are grateful to the trial participants who made this study possible.”
In March 2022, Krystal presented details on the Phase 3 study of B-VEC for the treatment of DEB, at the 2022 American Academy of Dermatology Annual Meeting in Boston, MA.
Among the findings, researchers found B-VEC treatment demonstrated a durable and statistically significant improvement in complete wound healing at three and six months compared to placebo.
Patients had a primary wound pair identified, and one wound was randomized to receive a weekly topical application of B-VEC and the other a placebo. The topical gel was applied weekly until the wound was completely closed. Subjects returned to the clinical site 30 days following the last dosing visit for safety evaluation by the trial investigator.
Krystal presented additional findings on safety and immunogenicity from the Phase 3 trial at the Society for Investigative Dermatology 2022 Annual Meeting, May 2022, in Portland, OR. Among the findings, researchers noted B-VEC was generally well tolerated, and the study resulted in no treatment-related discontinuations.
Earlier Studies Show Positive Results
Earlier Phase 1 and 2 clinical trials identified the optimal dose and frequency of which to apply B-VEC for wounds to close. These studies also looked at different formulations of the gels, and different kinds of the wounds that could be treated.
“We had to make sure the gel was durable, since wound size and shape can vary so much,” Krishnan said.
As with the Phase 3 trials, the earlier studies showed that repeat topical applications of B-VEC was associated with durable wound closure, along with evidence COL7 protein addressed the underlying molecular defect expression.
As skin cells and COL7 protein turnover and wounds open or as new wounds form, B-VEC can be reapplied as necessary to maintain wound closure. COL7 was found in skin that covered the healed wounds.
The Reality of Living with DEB
DEB affects roughly 3,000 people the United States. There currently is no cure for the disease, nor are there any effective FDA-approved therapies to alleviate symptoms. Life expectancy for patients with DEB is only about 30 to 35 years.
The wound burden of DEB patients can be body-wide and cause a host of other serious medical and psychological issues, including frequent surgeries needed to correct deformities. The physical pain of DEB is severe, and patients often are left feeling hopeless.
“The current approach is basically palliative care—in this instance, like the care burn victims receive,” Krishnan said. “It involves a lot of bandages and antibiotics, and wound care to prevent infection. There’s so much stigma around this awful disease, and I personally want to spread awareness around it.”