Amy Paller, MD: What Pz-cel, B-VEC Each Bring to Recessive DEB

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Gene and cell therapies are reaching patients with the severe forms of epidermolysis bullosa. An expert explains their differing benefits and strengths.

Amy Paller, MD: What Pz-cel, B-VEC Each Bring to Recessive DEB

Amy Paller, MD

The American Academy of Dermatology (AAD) 2024 Annual Meeting in San Diego, CA, this year comes with a flurry of exciting new developments in topics of rare skin disease management—more specifically, a number of marketing breakthroughs for new treatments, including some available and prospective gene and cell therapies.

The news should frequent discussions hosted inside and out of sessions at both AAD 2024 as well as the Society for Pediatric Dermatology (SPD) 2024 Pre-AAD Meeting in San Diego this week. A recurring question throughout those discussions may be, “How should we practice with these new products?”

In the first segment of a Q&A with HCPLive, Amy Paller, MD, chair of dermatology at Northwestern Medicine, discussed her particular interest in the recent development of therapies to treat dystrophic epidermolysis bullosa (DEB)—more specifically, the recently approved beremagene geperpavec (B-VEC; VYJUVEK) and the anticipated prademagene zamikeracel (pz-cel).

HCPLive: We've seen a great deal of development in dermatologic genetic disorder treatments of late; these are particularly beneficial for the pediatric patients, of course. Which of these disease spaces stand out to you as having some of the best good news of late?

Paller: I think the 2 major groups of disorders, when we're talking about genetic diseases, are EB and ichthyosis—and there's development going on in both of them. We're excited this year that we had the real breakthrough of having the first gene therapy (B-VEC) for a skin disease, for DEB. And it's an interesting form. It's not the kind of thing you might think about, where you're introducing a gene and then it's there forever. It's really using gene therapy to turn our own skin into a factory for making a drug—in this case, the drug being type VII collagen.

And it's really done a very nice job, in terms of the results from trials for patients, particularly in recessive DEB, the very severe form, which needs it the most. And that's now on the market with a pretty hefty price tag—but of course, some pretty exciting results.

HCPLive: Could you help describe particularly what the younger patients are experiencing before this would be a theoretical approach to care? What exactly is DEB manifesting as, symptom-wise?

Paller: Let's focus on recessive DEB, because that's what this is primarily used for. A baby is born often with several blisters and just spontaneously develops a lot more blisters—and on top of that, the blisters can be in the mouth, becoming very difficult sometimes to even eat without having pain. We can have blisters in the eyes as these young children grow up. It's one blister after another blister, after another blister. And they heal, but of course, when they're there, they're painful and itchy, and they can take some time to heal—they can take weeks to heal.

As we start to get older, we see more and more inflammation and still that tendency to make blisters, but a slower healing process as you get older. Of course, the deficiency in type VII collagen affects both the adhesive properties of skin—because it is a major component of the anchoring fibrils...but also collagen VII can be involved as an extracellular matrix component that cells can migrate on. There's so many reasons why it's problematic.

On top of that, this is deep enough that when people are healing, they're healing with scarring. Of course, repeated scarring which occurs particularly on arms, hands, legs and feet, is an increased risk factor for the development of cancer. And those patients who don't succumb early on in these really quite miserable lives of pain, itch and suffering to infections and some of the issues associated with their increased metabolic needs and a variety of other issues, often succumb to the development of not just the squamous cell carcinoma that somebody gets who's been out in the sun too much, but rather a really aggressive form of cutaneous squamous cell carcinoma that frequently metastasizes locally and beyond, and leads to large resections, amputations, and the leading cause of death.

HCPLive: It's good to address on that progression risk, because it certainly seems that's the overarching factor in care strategies.

Paller: Now, we don't know with his very first drug out whether there's going to overall be less scarring, but you got to think that if, on the one hand we can get things healing faster, and on the other hand if there is some persistence of effect that over time reduces the tendency to blister, that we may see less of that scar tissue. That remains to be seen.

And certainly, what's very important for these patients and their families is reducing the discomfort.

HCPLive: With regard to this other agent in development that we're anticipating an FDA decision in the first half of this year—pz-cel: Is there any disparity that we see in clinical outcomes that would differentiate it as an option compared to this other agent available for RDEB?

Paller: I think we're going to be using them in somewhat different ways. For example: it's really tough to put on a topical every week for a large area that's not healing. Contrast that to taking someone to the operating room and putting on multiple little patches of individually transformed cells that will sit there and hopefully cover them for 6 months to years for the most part, without breaking down in the same way. It may also depend on age; I think that the patients who were younger are such great candidates for the topical gene therapy. They don't have larger areas, they have more stem cells, they heal faster to begin with, and I think have had that much more of a response with the topical.

Aging, older individuals and those maybe a little bit slower in general to heal, those who have more of these larger areas, maybe are really who we would more readily designate for these transplants. And obviously, there may be those who can't be putting on (the topical) every week, because it's complicated, right?

So, I think there's going to definitely be a position for this, and we'll learn more about it. The more experience we have, the more we can see problems, as well as benefits of these various agents.

I will mention there is a new topical that just got approved that's just a general wound healer, that's the birch bark one. And we can throw that into the mix too. It's something that people don't have a nurse come and visit; they can have it at home, they can put it on the wound as soon as it comes out.

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