Emerging Treatment Options in AD

Raj Chovatiya, MD, PhD: I love that learning machine analogy very much because it is not just sending a combination of letters and numbers to classify your patient and get you where you need to get. Now, much as we started this discussion, where Matt told us there hasn’t been anything he’s been able to incorporate in his practice that has true predictive power, I am hoping this changes in the future, and you could get a set of patient characteristics, plus some clinical outcomes and what you see, and understand what might be the optimal choice for safety and efficacy. We’re not there yet, and it probably still won’t be a vending machine, but I look forward to that day. In that vein, in the last few minutes of this discussion, I’d love to look forward, that’s the fun part now, looking at things in various phases of trials for atopic dermatitis. Maybe we can go in a circle, and everyone can mention what either MOA [mechanism of action], ongoing trial, or even potential targets are exciting to them, and let’s start with you, Omar. If there’s one thing you’re looking forward to over the next 5 to 10 years, what is it?

Omar Noor, MD: What I’m excited about, and I love this concept because with atopic dermatitis, which we’ve established to be a heterogeneous condition that is still complicated, we’re still learning, we’re still getting better to make sure we have more options for our patients. I’m excited about nemolizumab, which is a biologic that’s going to be targeting IL-31 [interleukin-31]. We know that the cytokine IL-31 is specifically associated with neuronal cells targeting itch, and we see these patients. My patients who are not doing well in whatever therapy they’re on, they’re just sitting there, or a new patient, and they’re scratching. We know that itch-scratch cycle promotes a lot of disease processes, and if we can target something unique, like IL-31 in neuronal cells, I’m very excited to see how that’s going to affect our patients with atopic dermatitis, as well as a lot of other disease states that are itchy for our patients.

Raj Chovatiya, MD, PhD: Yes, a nice summation. And IL-31, which nemolizumab targets, right now it’s approved in Japan for pruritis associated with atopic dermatitis. It’s a unique label in terms of how that is, and to your point, we and others have published about this idea, that just because somebody has a low burden of lesions on their skin, they can still be extensively itchy, even if you’ve gotten disease control. So, taking a deeper dive into that itch, neuronal, neuroinflammation access is definitely something that excites me too. How about you, Adelaide, what’s the thing you’re looking forward to in the next few years, knowing that many of the treatments haven’t necessarily even got to those young children yet?

Adelaide A. Hebert, MD: I am going to focus on 2 arenas, and I’ve been very privileged to be a clinical investigator in both the tapinarof and the roflumilast studies, and we are studying these down into very young age groups. Granted, these patients are sometimes in double-blinded environments, so I can’t 100% assume they’re on the medication. But we have seen amazing results. We did in one of these clinical trials have an open-label portion, so I did see children who would come in covered with Band-Aids, bleeding from their scratching, and the mother would come in in tears. We transformed not only this child but this family by using these products. Again, in this open-label study, it was very dramatic, not only for me but also for the parents. We think these are going to be wonderful medications, and we really hope they get on the market very soon, because these children are suffering terribly, and because we have more limitations in what’s available for the pediatric population. This will really expand our options and help us care for these patients in such a great way. I also have to share with my adult dermatology colleagues, I think it’s one of the things you can say when it’s approved by the FDA in a very small age group, that’s a testament to the safety of these drugs. I know you probably explain that to your older patients, that if the FDA is letting us use it in the youngest, most vulnerable patients with broken skin, certainly we should feel safe about using them in older patients who come and need care.

Raj Chovatiya, MD, PhD: Those are nice points, I love it. How about you, Matt? I know there’s probably a long list, but what’s the one thing you’re most excited about?

Matthew Zirwas, MD: I think the one I’m most interested in is the one that’s just on the cusp of starting. I’m doing a proof-of-concept study with this company, and it is called a reactive aldehyde species inhibitor. Essentially what it’s doing, as part of our normal inflammatory response, we generate these reactive aldehydes that then covalently bind to various things in cells, proteins in cell membranes, then cause dysfunction. There also are environmental aldehydes that can get into our skin and then cause cellular damage or irritation. And so, this is a drug that’s already been approved or at least finished phase 3 trials as an eye drop. But we’re studying it as a systemic agent for psoriasis and atopic dermatitis, because what we’ve lacked in general is a systemic anti-inflammatory that is not also an immunosuppressant. That’s what this is hoping to be.

So, it’s the equivalent of ibuprofen for your skin, where you take ibuprofen and it’s anti-inflammatory but it’s not immunosuppressant, it just unfortunately doesn’t work on your skin. But to have something like that, a totally different mechanism that we’ll be able to explain to patients as, “This is neutralizing toxins that your body is generating.” Patients will love that terminology, “Toxins, your body generates toxins, and there are environmental toxins and we’ll get rid of those toxins.” The only thing that would be better is if it was natural. “We’re going to naturally get rid of those toxins,” would be even better. “But toxins, we’re going to neutralize the toxins.” I’m excited to see if it’s going to work.

I know I was only allowed one, but the other one I’m excited about just because it’s going to be so different is the OX40 drug that’s going into phase 3 clinical trials. What’s exciting about that one, it looks like it works slower than other drugs, but in some of their phase 2 data, of the people who got to EASI-75 [75% reduction in the Eczema Area and Severity Index], 80% of them were still at EASI-75 20 weeks after their last dose. So, it really puts a high number of people into durable remissions. But there’s a cost to that, which is it takes a little longer to work. There’s the cost-benefit of, “Well, you’re going to have to suffer a bit longer before your itch starts getting better. But once you get better, we may be able to put you into a very durable remission,” which would be phenomenal.

Raj Chovatiya, MD, PhD: We’ll end this segment with you, Peter. Is there anything in particular that really excites you, knowing how much activity is in the space?

Peter A. Lio, MD: I love what my colleagues said, there’s so much great stuff. The one that I feel is maybe the next big frontier that we’re just starting to enter is the microbiome. I’m fascinated by prebiotics, probiotics, symbiotics, parabiotics, postbiotics, and all these other ways to manipulate the microbiome that are not just slamming it with an antibiotic, which is all we’ve really had, or using diffuse antiseptic agents. So really being able to manipulate this. I’m not a betting guy, but I would put some money on the fact that if we can fix the microbiome, we might see all these other pieces fall into place. Because the microbiome is playing a role, even in ways I don’t think we fully appreciate yet. And Raj, before we wrap up, I want to turn it back to you. What are you excited about as our fearless leader and moderator today?

Raj Chovatiya, MD, PhD: I’m glad you asked. I would have said so anyway even if you didn’t care to hear what I had to say. But I think one of the coolest things is, we’re beginning to understand that because atopic dermatitis is so heterogeneous, perhaps a single target is not going to be the answer for therapy ongoing. There’s a lot of cool science going on about how you design bivalent targets, antibodies that have multiple heads, molecules that could target 2 different things at once, and hit 2 opposite types, inflammation and disease. I think that is what excites me the most, the fact that we might be able to fine-tune our responses and get beyond some of the walls we’ve hit when it comes to maximum responses for even our best therapies right now.

Transcript edited for clarity