Novel Therapy Shown Effective for Atopic Dermatitis

ORLANDO, Fla. — In a phase 3 atopic dermatitis (AD) trial, rocatinlimab, a novel therapy that targets T cells expressing the OX40 receptor, showed efficacy on both coprimary and key secondary endpoints in treatment-experienced patients with long-standing moderate to severe disease.

The efficacy of the drug appears to be derived from its ability to eliminate activated T cells driving AD without inhibiting other T cell types, according to Emma Guttman-Yassky, MD, PhD, professor of dermatology and immunology, and chair of the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York.

“Rocatinlimab is a potential new medication that works differently than existing atopic dermatitis medications,” Guttman-Yassky said at the American Academy of Dermatology 2025 Annual Meeting, where she presented the phase 3 results in a late-breaker session.

Other Diseases Might Share the OX40 Receptor Target 

The effect of targeting only T cells expressing the OX40 receptor in AD, a T helper 2 (Th2)–mediated inflammatory disease, might be relevant to other Th2-mediated disorders, Guttman-Yassky speculated.

The trial she presented, ROCKET HORIZON, is part of a seven-trial development program with rocatinlimab in AD. Four of the trials are enrolling adults. Three are enrolling patients aged 12-18 and some of the trials are evaluating this agent in combination with other AD therapies. Eventually, more than 2000 patients will be enrolled with follow-up extending up to 104 weeks.

In ROCKET HORIZON, 726 patients were randomly assigned in a 3:1 ratio to rocatinlimab or placebo, both administered as a subcutaneous injection every 4 weeks after a loading protocol. The dose of rocatinlimab was 300 mg.

The coprimary endpoints at 24 weeks were a Validated Investigator Global Assessment for atopic dermatitis (vIGA-AD) score of 0 or 1 (clear or almost clear) and a 75% reduction or greater in the Eczema Area and Severity Index (EASI)-75 score. Secondary endpoints included EASI-90 and change from baseline in itch as measured with the Worst Pruritus Numerical Rating Scale (WP-NRS).

In the primary analysis, any patients who used rescue therapy were considered nonresponders, but a prespecified, as-observed sensitivity analysis was performed to include those excluded for taking rescue therapy, Guttman-Yassky reported.

At week 24, EASI-75 response rates were 32.8% and 13.7% in the rocatinlimab and placebo arms, respectively. In the as-observed sensitivity analysis, the rates were 46.6% and 15.8%, respectively (both P < .001 in favor of rocatinlimab).

The proportion of patients with a vIGA-AD response of 0 or 1 was 19.3% vs 6.6% (P < .001) in the primary analysis. In the as-observed group, these rates were 24.1% vs 6.6% (P < .001).

The proportion of patients who achieved EASI-90 was about fourfold greater in the primary analysis (19.9% vs 4.9%; P < .001) and the as-observed analysis (26.3% vs 5.5%; P < .001), Guttman-Yassky reported, noting that the use of rescue therapy did not dilute the relative advantage of rocatinlimab.

Substantial Itch Relief Reported

The proportion achieving at least a four-point reduction from baseline in the WP-NRS score was about two times higher in both the primary (24.0% vs 10.5%; P < .001) and in the as-observed (32.9% vs 18.5%; P < .001) analysis.

Response scores were still improving at the end of the 24-week study, permitting “a potential for additional efficacy with longer follow-up,” Guttman-Yassky said.

In support of the mechanism, a steep drop in CD4+ T cells positive for the OX-40 receptor was observed in the active treatment arm throughout the study. Conversely, there was no change in CD4+ T cells without this receptor.

Calling rocatinlimab generally well tolerated, Guttman-Yassky noted that serious adverse events (1.8% vs 4.4%) were less common in the active-therapy arm.

The median duration of AD in the ROCKET-HORIZON study was approximately 25 years. Over the course of their AD, the majority had been treated with at least one systemic therapy, and more than 20% had been treated with a biologic or Janus kinase inhibitor, Guttman-Yassky reported.

At baseline, nearly 40% had severe disease (vIGA-AD score, 4), and the remainder had moderate involvement (vIGA-AD score, 3).

“All primary and key secondary endpoints were met in a diverse treatment-experienced AD population with moderate or severe disease,” Guttman-Yassky said.

Importantly, although more data will soon be available to further explore the safety and efficacy of this drug, the reduction in OX40 receptor–positive T cells is consistent with the premise that this agent might introduce an entirely new mechanism for the control of AD.

Identifying new potential mechanisms of action for inflammatory skin disease is always intriguing, but Paul T. Ngheim, MD, PhD, director of the Skin Oncology Clinical Program at Fred Hutchinson Cancer Center, Seattle, Washington, was particularly interested in seeing the benefit of hitting a target that failed in a different skin disease.

“I found it fascinating,” Ngheim said in an interview. In this trial “we are newly seeing the clinical activity of targeting the OX40 receptor, a pathway that was entirely ineffective in psoriasis yet is now highly active in AD.”

While the data are positive for AD, he is also interested if the same target might prove more broadly applicable.

As a proof of concept in AD, “it thus represents a significant and distinct mechanism of immune modulation with promise for other Th2-mediated diseases,” he said.

Guttman-Yassky reported financial relationships with more than 55 pharmaceutical companies, including Kyowa Kirin, which is developing rocatinlimab. Ngheim reported financial relationships with Almirall, Bristol Myers Squibb, EMD Serono Inc., Merck, and Pfizer.