Key atopic dermatitis approvals are changing the treatment landscape

2024 was a big year for the atopic dermatitis (AD) treatment landscape, with several key approvals from the FDA putting new formulations, advanced systemic therapies, and topicals into the toolbox for pediatric health care providers.

Following, we have snapshots of key approvals from 2024 followed by expert commentary from Lawrence Eichenfield, MD, and Russell Libby, MD, FAAP, who explain what kind of positive impact these new treatments can have on a vulnerable population of pediatric patients with AD. In addition, Eichenfield explains the overall changing treatment landscape for AD and what pediatricians should know about these newly approved agents.

Eichenfield is professor of dermatology and pediatrics and chief of pediatric and adolescent dermatology at Rady Children’s Hospital in San Diego, California. Libby is an editorial advisory board member of Contemporary Pediatrics, founder of Virginia Pediatric Group, and assistant clinical professor of pediatrics at the University of Virginia School of Medicine in Charlottesville.

Drug: tapinarof cream 1% (Vtama)

Manufacturer: Organon

Quick facts¹:

· Approved on December 16, 2024

· Indicated for AD in patients 2 years or older

· Steroid-free, once-daily aryl hydrocarbon receptor agonist

Key study data:

In the ADORING 1 clinical trial (NCT05014568), adult and pediatric participants 2 years or older with moderate to severe AD were randomly assigned 2:1 to receive once-daily tapinarof or vehicle cream. By week 8, 45.4% of participants who received tapinarof achieved the primary end point of a Validated Investigator Global Assessment for AD (vIGA-AD) score of 0 or 1 with at least a 2-grade improvement from baseline. In the trial findings, 55.8% of tapinarof users achieved the key secondary end point of the proportion of participants with a 75% or greater improvement in the Eczema Area and Severity Index-75 score from baseline at week 8 (P < .0001).²

“It’s rare to have a steroid-free option but also to have something that’s going to work in a completely different mechanism. Instead of just blocking inflammation, with tapinarof, we’re seeing the epidermal barrier, so your skin integrity improves with it.” —John Browning, MD, MBA, FAAD, FAAP, board-certified pediatric and adult dermatologist in San Antonio, Texas; assistant professor at the Baylor College of Medicine in Houston, Texas; as well as chief of dermatology at the Children’s Hospital of San Antonio.¹

Drug: roflumilast cream 0.15% (Zoryve)

Manufacturer: Arcutis Biotherapeutics

Quick facts³:

· Approved on July 9, 2024

· Indicated for mild to moderate AD in adults and children 6 years or older

· Once-daily, steroid-free topical formulation of a highly potent and selective phosphodiesterase 4 inhibitor

Key study data:

The approval was based on data from the INTEGUMENT-I (NCT04773587) and INTEGUMENT-II (NCT04773600) trials, which met the primary end point of IGA success (defined as vIGA-AD score of clear or almost clear plus a 2-grade improvement from baseline at week 4).⁴

· INTEGUMENT-I: 32% roflumilast cream vs 15.2% vehicle (P < .0001)⁴

· INTEGUMENT-II: 28.9% roflumilast cream vs 12% vehicle (P < .0001)⁴

Drug: nemolizumab (Nemluvio)

Manufacturer: Galderma

Quick facts⁵:

· Approved on December 13, 2024

· Indicated for patients 12 years or older with moderate to severe AD in combination with topical corticosteroids and/or topical calcineurin inhibitors when disease is not adequately controlled with topical prescription therapies

· First approved monoclonal antibody specifically targeting IL-31 receptor α, inhibiting the signaling of IL-31 (a neuroimmune cytokine that drives itch and is involved in inflammation and epidermal dysregulation in AD)

Lawrence Eichenfield, MD | Rady Children's Hospital

Contemporary Pediatrics:

What is your reaction to the FDA approval of tapinarof cream 1%?

Lawrence Eichenfield, MD:

Remember that this is the first approval for tapinarof for AD. We get from age 2 upward through adults at the same time with the same formulation [for which] we’ve had experience with psoriasis. The safety looked quite good in the pediatric patients as well. Tolerance was quite good. Efficacy looked quite good as well. There’s this uncommon follicular event, folliculitis, but that seemed to be not greater in AD, might have been a little less. So that was nice from a safety standpoint. It’s exciting to get newer nonsteroidals in our hands. We certainly have patients who are very concerned about topical corticosteroids and many patients [whom] we can’t necessarily treat with just topical corticosteroids long term, so tapinarof comes in with that mixture of the short-term studies and longer-term studies intermittently, giving us a nice, effective alternative nonsteroid for eczema across the ages.

Contemporary Pediatrics:

Can pediatricians feel comfortable prescribing tapinarof cream 1%?

Eichenfield:

We have work to do to get pediatricians comfortable. We’re in this newer age of having alternative, nonsteroidal medications and, at the same time, this incredible knowledge about the need for long-term disease control and eczema to both increase the chances that it may get better over time in those patients [with] mild [disease], sometimes with spontaneous remission, and also minimize the disease impact and potentially the worsening of the disease and development of comorbidities. So my message out to pediatricians? Yes, learn about the newer nonsteroidals. It could help them to expand their management of patients who are in their hands and those [whose disease] they might be able to get under good control without the need for [an] allergist or dermatology specialist.

Contemporary Pediatrics:

What is your reaction to the addition of nemolizumab since it was approved in December 2024?

Eichenfield:

I’m excited to get the approval of “nemo,” so to speak. We’ve been waiting a while there, because that drug has been in development over several years and first got approved in the Japanese market for its association with AD and then for prurigo nodularis in adults. Now we have its approval [in those patients] 12 [years or] older [in the United States]. It’s a totally novel drug [in] that it’s [blocking] cytokines, so…IL-31 is an important player in pathophysiology of AD. This gives us another systemic biologic, and we’ll see how it plays out in terms of sequencing or relationship to other biologics. Of course, we have oral JAK inhibitors as well in that same age group of patients 12 [years or] older. In dealing with a lot of people who’ve had experience with nemolizumab in the clinical trials and then with prurigo nodularis in some cases overlapping with AD, people have these stories of incredible responsiveness that seem to be different than with other biologic agents. That’s what we’ll be figuring out over the next months to years, as we have this newer, totally different type of biologic in our hands.

Russell Libby, MD, FAAP

Contemporary Pediatrics:

What are your thoughts on the FDA approval of roflumilast cream 0.15% for AD?

Russell Libby, MD, FAAP:

First, when we look at AD, it’s a chronic problem. You certainly start in infancy to a great degree, but even somewhere between 7%...or 10% of kids will have episodic [eczema], and some of them [will have] rather severe and chronic eczema. Having another medication you can use that can help address the issue for the kids [with] more chronic [eczema] is always helpful. We get nervous using steroids all the time, especially as they get more potent, and parents worry. They don’t know what regimen to use, they don’t know how to maintain sometimes, and it gets difficult. Now dupilumab (Dupixent) has come along, and for those with the chronic issues, it has been a godsend for those with severe and ongoing chronic AD, but nonetheless, there are those who [have] less severe [eczema] and don’t want to go on immune suppressants and are looking for topicals. What I can see reading about roflumilast is that it is a better-tolerated medication. It has the same kind of impact on one of the pathways in the inflammatory routine, but it seems to have a pretty good response.

Contemporary Pediatrics:

Can you speak to the overall changing landscape when it comes to AD, and what are the biggest takeaways for primary care providers?

Eichenfield:

We still have this incredible revolution in care of AD. We have our newer nonsteroidals in our hands. We have additional biologic agents. Tralokinumab got approved [for those aged] 12 [to 17 years], adding to our regimen. Lebrikizumab got approved [on September 13, 2024], for [those] 12 years [or] older. We have this incredible data set on dupilumab that has been coming out in both placebo-controlled trials, and in long-term registry trials and these database studies, [findings are] all seemingly showing that in patients treated with dupilumab in the younger ages, [there is] a decrease in the development of asthma and allergic rhinitis. [We’re observing] this trend toward disease modification in terms of impact on development of comorbidities. That’s very exciting. At the same time, we have more steroid phobia than we’ve ever had with people who’ve used small amounts of topical steroids thinking they may have steroid withdrawal or steroid addiction, which is not to say that’s not a real phenomenon. It is truly a phenomenon, but we have patients who believe they might have that who’ve never been in a situation where they’ve used enough topical corticosteroids for that to be the phenomenon, and they just have persistent eczema in some cases. So we still have a lot of work to do in taking care of our population. But the different tools that we have now put us in a much better situation to manage AD and potentially minimize complications over time.

My messaging to pediatricians, as I did full pediatrics training years ago at CHOP [Children’s Hospital of Philadelphia] [in Pennsylvania] before I went on to dermatology, is I don’t expect them to be writing biologics for AD but I want them to recognize the incredible life changes that we can bring with our newer topicals and systemic agents. If they have tough patients, recognize that the time of waiting for children to outgrow their eczema. If they have very mild disease, that can be managed with moisturizers and a few topicals now or then over the year, that’s fine. But for more significant disease, go ahead and get comfortable using more of the topicals and then be liberal and send patients for evaluation for systemic agents, because the difference is now the risk-benefit of our new, advanced systemic therapies. They’re incredibly beneficial and life-changing with very little risk compared with our traditional immunosuppressives. Getting them warmed up and ready makes sense.

References:

1. Fitch J. FDA approves tapinarof cream, 1% for atopic dermatitis patients 2 years and up. Contemporary Pediatrics. December 16, 2024. Accessed January 8, 2025. https://www.contemporarypediatrics.com/view/fda-approves-tapinarof-cream-1-for-atopic-dermatitis-patients-2-years-and-up

2. Dermavant reports positive topline results from ADORING 1, the second atopic dermatitis phase 3 trial of VTAMA (tapinarof) cream, 1% in adults and children as young as 2 years old. News release. Dermavant Sciences. May 16, 2023. Accessed January 8, 2025. https://www.dermavant.com/dermavant-reports-positive-topline-results-from-adoring-1-the-second-atopic-dermatitis-phase-3-trial-of-vtama-tapinarof-cream-1-in-adults-and-children-as-young-as-2-years-old/

3. Fitch J. FDA approves roflumilast cream 0.15% for atopic dermatitis in patients aged 6 years and up. Contemporary Pediatrics. July 9, 2024. Accessed January 8, 2025. https://www.contemporarypediatrics.com/view/fda-approves-roflumilast-cream-0-15-atopic-dermatitis-patients-aged-6-years-older

4. FDA approves Arcutis’ ZORYVE (roflumilast) cream 0.15% for the treatment of atopic dermatitis in adults and children down to 6 years of age. News release. Arcutis Biotherapeutics Inc. July 9, 2024. Accessed January 8, 2025. https://www.arcutis.com/fda-approves-arcutis-zoryve-roflumilast-cream-0-15-for-the-treatment-of-atopic-dermatitis-in-adults-and-children-down-to-6-years-of-age/

5. Galderma receives U.S. FDA approval for Nemluvio (nemolizumab) for patients with moderate-to-severe atopic dermatitis. News release. Galderma. December 13, 2024. Accessed January 8, 2025. https://www.galderma.com/news/galderma-receives-us-fda-approval-nemluvior-nemolizumab-patients-moderate-severe-atopic