Why Less Frequent Dosing May Matter With Long-Acting IL-13 Biologics

During the recent American Academy of Dermatology (AAD) annual meeting, MedPage Today brought together three expert leaders for a virtual roundtable discussion on atopic dermatitis: Moderator Peter A. Lio, MD, of Northwestern University Feinberg School of Medicine in Chicago, is joined by Sarina B. Elmariah, MD, PhD, of the UCSF Center for Itch and Neurosensory Disorders in San Francisco, and Jennifer Soung, MD, a dermatologist and director of clinical research at Southern California Dermatology in Orange County.

This episode focuses on long-acting interleukin (IL)-13 biologics and what less frequent dosing could mean for efficacy, durability, and disease modification.

Following is a transcript of their remarks:

Lio: Hello, everyone and welcome to our roundtable on some of the exciting new news on atopic dermatitis that came out of the recent AAD meeting in Denver, Colorado. I’m Peter Lio. I’m a clinical assistant professor of dermatology and pediatrics at Northwestern University Feinberg School of Medicine in Chicago, Illinois. I’d like to introduce my colleagues, first of all, Dr. Soung.

Soung: Hi, everyone. I’m Jennifer Soung. I am a dermatologist and clinical researcher from Southern California Dermatology and clinical faculty at Harbor-UCLA [Medical Center].

Lio: And Dr. Elmariah.

Elmariah: Hi, everyone. I’m Sarina Elmariah. I’m a dermatologist and professor of dermatology at the University of California San Francisco.

Lio: Thank you both so much for being here with me today. First thing, we know that this is an incredibly exciting time in atopic dermatitis. In fact, it’s so exciting that we’re kind of overwhelmed. There’s so many things happening. We don’t know where to begin.

I thought maybe somewhere we could start is talking about zumilokibart, and this is sort of a technological advancement in our biologics. And what’s really neat is they use a technology called YTE that actually affects the Fc portion of the antibody to allow it to be recycled. So instead of needing to dose things every 2 weeks or 4 weeks, it looks like we might be able to dose things every 3 months to every 6 months — maybe even beyond that, it depends. But it’s so exciting to see this. And this is a technology that potentially has repercussions because it seems like the first drug that we’re going to see is really an IL-13 blocker.

We have some other drugs in that class already, but this one would potentially have this extended dosing, which might have other changes for us. I’d love to just start there and get your thoughts and feedback on that.

Soung: That data really struck me when I saw the presentation at AAD, where one, it really showed that IL-13 is one of the key cytokines where about 75% to almost 86% of patients are getting clear or almost clear. And we’re talking about dosing at every 3 to 6 months, so that kind of surprised me. Wow, less dosing and deepening of response, so reinforcing that we’re on the right pathway in terms of targeting IL-13 alone, too.

Many times atopic dermatitis can be really tricky to treat because every patient has a different phenotype. And certainly we see different responses, for example, when we compare a biologic to a JAK inhibitor where we’re targeting multiple cytokines. However, this was interesting because now I’m learning that, wow, there’s definitely these patients who have a strong IL-13 presence. And so these higher responses and longer and deeper responses are great for patients.

Elmariah: Yeah, I would also comment there’s a lot of excitement, I think, around zumilokibart and the APEX studies. There were a couple of things that were interesting about their design. It was front-loaded in terms of dosing a little bit more frequently upfront, but that allowed this, again, up to every 6 months, so Q24 week dosing with persistence in that EASI-75 [a 75% reduction from baseline in the Eczema Area and Severity Index] by week 52.

The other thing is that over 40% of these patients got to EASI-100 [a 100% reduction from baseline in the EASI] by week 52. And the fact that we’re even talking about EASI-100 and having what almost seems like a true remission on drug with infrequent dosing is really impressive. And, actually, because of the design of this molecule, I guess, there really is even some degree of superiority even to existing biologics and JAK inhibitors that we already use. So, that’s pretty fantastic.

And I would also say, just in general, in the 52-week study, there were very few serious AEs [adverse events], a little bit of conjunctivitis that we have to be aware of, around 14%, so we know that might be an issue.

But back to Jennifer’s point, IL-13 is critical to the elaboration of inflammation in the skin and AD [atopic dermatitis]. And so this, I think, addresses that aspect of it with this tremendous potential for a reduced dosing frequency. Really, really exciting stuff.

Lio: I love it. And I think you guys really bring up all these key points. It’s not just the convenience. The convenience is great, and that’s sort of, on its face, what it seems like the big breakthrough is, but there may be more disease modification or changes in the pharmacokinetics just because it is really a different set of dosing that actually means the drug is in our body for much longer.

Now, I’ll just point out because people will say it, the trade-off for that, of course, is if there’s an adverse event, then you of course have patients who now have to potentially be exposed to something causing an adverse event for much longer. So there is a risk-benefit. But with something like IL-13, we already have a lot of experience with it. We feel pretty comfortable with it overall.

So, my sense is that this is going to be a breakthrough not only for the dosing, but also potentially for the ability to do some changes and modification in the disease.