The FDA has approved Krystal Biotech's beremagene geperpavec (B-VEC) (Vyjuvek; Krystal Biotech) to treat the wounds of dystrophic epidermolysis bullosa (DEB) patients aged 6 months and older. B-VEC is the first FDA-approved gene therapy treatment for DEB, according to the agency. In this Contemporary Pediatrics interview, Raj Chovatiya, MD, PhD, breaks down this much-anticipated FDA approval.
Transcript (edited for clarity)
Contemporary Pediatrics®:, Raj Chovatiya, MD, PhD, Chovatiya:
Hello and thank you so much for joining us. I'm Joshua Fitch, editor of Contemporary Pediatrics.
Raj Chovatiya, MD, PhD
Hi there. My name is Dr. Raj Chovatiya, assistant professor of Dermatology and director of the Center for Eczema and Itch at Northwestern University Feinberg School of Medicine in Chicago, Illinois.
Thank you so much for joining us. Today we're discussing the FDA approval of Krystal Biotech's B-VEC for the treatment of dystrophic, epidermolysis bullosa, or DEB, for patients 6 months and older. How can this option for DEB patients affect the overall treatment landscape now that this has been FDA approved?
Great question. And I think that to really understand the effect, the field really needs to understand the disease itself just so we can kind of understand what's been needed for so long. So very briefly, dystrophic epidermolysis bullosa is a pretty rare skin blistering disorder that results from mutation in the gene that encodes type 7 collagen and this disease can really place a lifelong burden on affected children and their caregivers. This is really not just the disease of a single individual, but really one that kind of requires an entire group or family committed to helping. And you can imagine that if you don't have type 7 collagen, you can't really have appropriate connection of the epidermis to the dermis. And so some of the problems in this disease include cutaneous blistering, following minor trauma, repeated cycles of blistering, scarring, malignancy, infection, limb loss, even early death. And so as of now, we haven't really had any targeted treatments for this disease. And most of our treatment approaches have really been based around supportive care. And so this just represents an immense move forward in terms of actual rational design of a treatment where we can actually make a big difference in individuals lives.
You kind of touched on the differences of current treatment processes. How does this treatment work, compared to other treatments currently approved. And we understand the process, this being a topical treatment, will be much smoother?
Absolutely right. In dermatology, if you can make something in a topical form and make it work? Well, it's a win-win, just given the fact that we're dealing with cutaneous diseases here. So typically, with treatment for dystrophic, epidermolysis bullosa, when I say supportive care, this includes wound care, optimal bathing, really controlling for potential infection, nutritional support, and even preventing and treating any particular complications. And so really, this can be a complex condition that requires an entire health care support team, which includes a dermatologist. So really a number of ways in which we can sort of help support the skin, but not any particular targeted treatments that can help with some of the blistering pain or other symptoms that are felt here. So there's been some work in the area of targeted treatments: cell-based therapies have been the one where there's been some promise potentially. But there's been some pitfalls too. So with bone marrow transplantation, there was a pretty high mortality rate that was seen in research, there was work done with trying to graft transduced cells that contained overexpression of type 7 collagen, intriguing idea, but really concerns around oncogenesis risk as well, given the fact that viral insertion sometimes can be unpredictable. So really, the idea of an approved targeted treatment and a topical form instantly places it above pretty much anything that we have at this point in time.
And obviously, even with a weekly administration process, a continuous weekly administration process, the burden for not only the patients 6 months and older but their families has to be immediately felt, how much of a difference can this make in a day to day treatment.
I mean, night and day, considering that most of our treatment approaches right now just include exercising not only immense caution for the skin, but a variety of ways when we're just trying to make sure that even if we have wounds, we're treating them, we're preventing them from getting larger, helping them to heal. And so if you actually have a treatment, where potentially you could prevent some of this, that is really just a game changer. And in the phase 3 clinical trials taking a look at the back what was found several different outcomes is that there was actual high levels of success and wound closure, pain reduction. And the key thing here is really promising safety low adverse events, and really no treatment related discontinuations suggesting to us that this is definitely better than the current approaches that we have right now.
Now, can you talk about the application process based on your research information from some of these phase 3 trials, exactly what it is, where it is directly placed on these wounds, and perhaps what it does not treat?
Sure, great question. So, you know, when we say topical, I think that part makes sense. It's gonna be a weekly administration also based on the way the trial was designed, but I think it's important to understand exactly what is being applied in the actual topical medication because this is a little different than a small molecule or biologic therapy that we've all become really used to in dermatology. So the important thing to note is that B-VEC is at topical gene based therapies. So this is kind of a novel thing for us. And this is really kind of an innovative approach. It modifies a herpes simplex virus, 1 vector. So this is a modified HSV one virus that limits the pathogenic aspects of the virus we don't want and non permanently delivers functional types of collagen. So why am I giving this preamble? Well, the cool thing about this modified virus is that you can deliver it to the skin, you can insert a pretty large payload in terms of the gene of interest. And you can actually repeatedly administer the medication without developing any immunogenicity or tolerability effects, something that is an issue with other types of gene-directed therapies. So really, this is the reason why weekly application is possible with this type of medication. I think it's important to understand, you know, even though I'm expressing a lot of enthusiasm and excitement, with any phase 3 study, there's always limitations and thus, more we hope to learn in the real world when individuals actually have access. So in the course of the B-VEC studies, remember that largely wounds were capped at a certain size in this study, so it wasn't really used for the most extensive wounds. Additionally, there was really only one patient in the study that had dominant dystrophic EB vs the more common recessive type, just knowing that there can be some heterogeneity in terms of the actual presentation, but I don't want that to damper kind of any of the enthusiasm here. I think this is stuff that will end up learning a bit more in the real world. But really, the takeaway point is that we finally have a highly efficacious, targeted, very easy to administer treatment for a genetic skin disease that really didn't have anything before.
FDA approves first topical gene therapy for treatment of wounds in patients with dystrophic epidermolysis bullosa. FDA. May 19, 2023. Accessed May 19, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-topical-gene-therapy-treatment-wounds-patients-dystrophic-epidermolysis-bullosa