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David Rosmarin, MD, reviews a quintet of promising agents advancing in late stages while at RAD 2023.
Systemic therapy development has been rapidly accelerated for fields like atopic dermatitis for years now—and in some cases, has been debated to be a bit difficult to keep organized in real-world care.1 Nonetheless, a boom of evidenced and unique topical agents in eczema may positively alter the prescriber strategy and provide patients more confidence in initiating and adhering to the right treatment for their heterogeneous disease.
At the Revolutionizing Atopic Dermatitis (RAD) 2023 Spring Conference in Washington, DC, David Rosmarin, MD, chair of the department of dermatology at Indiana University School of Medicine, reviewed 5 topical agents currently under development for atopic dermatitis—and how they may one day fit into the dermatology armamentarium pending US Food and Drug Administration (FDA) decision.2
Data supporting the topical PDE4 inhibitor was among the headline topics at the American Academy of Dermatology (AAD) 2023 Annual Meeting in New Orleans this March, when investigators from the INTEGUMENT trials showed approximately one-third of treated patients with atopic dermatitis achieved the primary endpoint of validated Investigator’s Global Assessment score for atopic dermatitis (vIGA-AD) scores of 0-1 after 4 weeks with once-daily roflumilast 0.15%.3
The agent is currently in development for patients aged ≥6 years old, Rosmarin said, while phase 3 assessment of a 0.05% concentration is ongoing in children aged 2-5 years old. It’s shown quick, symptomatic benefit for patients with eczema—while clinicians stay diligent on its safety and tolerability.
“It certainly helps with itch, it’s very rapid,” Rosmarin said at RAD 2023. “And in terms of safety, we have the crisaborole experience in our mind…we’re hopeful that roflumilast does not repeat that experience in real life, where we’re seeing almost 40% crisaborole application site reactions, and I think so far the experience in psoriasis has verified that.”
An aryl hydrocarbon receptor agonist, tapinarof 1% is supported by phase 3 ARDORING 2 trial data showing more than half of patients administered the once-daily topical achieved Eczema Area Severity Index 75% improvement (EASI 75; P <.0001) and/or a ≥4-point reduction in Peak Pruritus Numerical Rating Scale (NRS) scores (P <.0015) at 8 weeks.
Nothing from pivotal trial data implicates a safety or tolerability concern, Rosmarin said. Tapinarof 1% is being considered for patients with atopic dermatitis aged ≥2 years old, having shown a flexible capability in treating chronic skin disease through its unique mechanism of action.
“Not only does it downregulate cytokines in the Th17 pathway, which is why it is originally approved for plaque psoriasis, but it downregulates Th2 cytokines and also helps upregulate proteins in the skin barrier,” Rosmarin said.
Another potential addition to the Janus kinase (JAK) inhibitor class, delgocitinib has been reviewed in phase 3 data for the treatment of chronic hand dermatitis—a condition currently without an FDA-approved treatment option.
In the DELTA 1 trial, a twice-daily regimen of delgocitini was associated with an IGA score of 0-1—indicating clear or almost clear skin—in 19.7% of treated patients, versus just 9.9% in the vehicle arm, at 16 weeks. Noting the seemingly less impressive efficacy outcome, Rosmarin stressed the difficulty in treating hand eczema.
“These results are still meaningful for patients—it’s just that hands are harder to reach those endpoints. And they had a meaningful change in quality of life (per Dermatology Life Quality Index), and similar safety as we’re seeing from the topical JAK inhibitors.”
Touting it as a newcomer in the space, Rosmarin expressed caution in initial excitement surrounding the 5-Lipoxygenase (5-LO) inhibitor: zileuton 1% targets arachidonic acid pathways, a mechanism that which has led to shortcomings in atopic dermatitis treatment outcomes with prior agents.
Nonetheless, it touts phase 2A trial data showing a twice-daily regimen over 8 weeks helped 30% of treated patients achieve IGA 0-1 versus 4% of vehicle patients (P = .02). What’s more, patients showed response to the treatment in as soon as 2 weeks.
“The percent change in EASI score, though, was not that different between the 2 groups,” Rosmarin noted. “Again, this holds some promise, but we have to be cautious with this new pathway, and orally it’s not being developed so much because it causes LFT elevations in some patients.”
Phase 3 data from Korea show the twice-daily TRPV1 receptor antagonist provided skin clearance per IGA 0-1 to 36.0% of treated patients and resulted in a mean EASI reduction of 44.3% over 8 weeks—compared to outcomes of 12.8% and 21.4%, respectively, in the vehicle arm.
Though the late-stage research is limited as to uncertainty as to how it would apply to a US patient population, Rosmarin highlighted the drug’s promising safety profile.
“Hopefully this will be studied in the US as well,” he said.