TOPLINE:

Subcutaneous rocatinlimab, an investigational T-cell rebalancing therapy targeting the OX40 receptor, was effective and well tolerated in adults with moderate-to-severe atopic dermatitis (AD), in two phase 3 trials.

METHODOLOGY:

• Two global, 24-week, randomized, double-blind, placebo-controlled phase 3 superiority trials enrolled adults with moderate-to-severe AD: ROCKET-IGNITE (n = 760; mean age, 37.6 years; 59% men; 59% White) and ROCKET-HORIZON (n = 726; mean age, 38.4 years; 55% men; 60% White), at 168 and 151 sites, respectively, in 19 countries.
• Patients in IGNITE were randomly assigned in a 3:2:2 ratio to receive rocatinlimab 300 mg, rocatinlimab 150 mg, or placebo, while patients in HORIZON were randomly assigned in a 3:1 ratio to receive rocatinlimab 300 mg or placebo. Treatment was administered at weeks 0, 2, and 4 and then every 4 weeks through week 20.
• Primary endpoints included the Eczema Area and Severity Index (EASI)-75 response and a validated Investigator’s Global Assessment for AD (vIGA-AD) score of 0 or 1 (clear or almost clear skin) at week 24.
• Secondary endpoints included EASI-75 response and a vIGA-AD score of 0 or 1 at week 16; EASI-90 response at week 24; 4-point or greater reductions in numeric rating scale assessments (NRS) for worst pruritus (WP-NRS), and AD skin pain (SP-NRS) and the Dermatology Life Quality Index (DLQI) at week 24; a facial AD severity score of clear at week 24; and safety outcomes.

TAKEAWAY:

• A higher proportion of patients who received rocatinlimab (42% on the 300 mg dose, 36% on 150 mg) vs placebo (13%) achieved an EASI-75 response at week 24 in IGNITE (P < .001 for both). Similarly, in HORIZON, a significantly higher proportion of patients on rocatinlimab than those on placebo achieved an EASI-75 response (33% vs 14%; P < .001).
• At week 24, in IGNITE, a vIGA-AD score of 0 or 1 was achieved by 24% of patients in the rocatinlimab 300 mg group (P < .001) and 19% of those in the rocatinlimab 150-mg group (P = .002) compared with 9% of patients in the placebo group. In the HORIZON trial, 19% of patients in the rocatinlimab 300-mg group vs 7% in the placebo group achieved this score (P < .001).
• At week 16, the proportions of patients achieving EASI-75 response and a vIGA-AD score of 0 or 1 were higher in the rocatinlimab group (P < .001 for both). Score reductions of 4 or greater in the WP-NRS, SP-NRS, and DLQI and higher EASI-90 response rates at week 24 were observed with 300 mg and 150 mg rocatinlimab vs placebo, including a greater proportion of patients with facial clearance of AD (P < .001 for all comparisons).
• The incidence of treatment-emergent adverse events was similar between groups in both trials, ranging from 2%-5% in patients treated with rocatinlimab and 4%-6% in patients on placebo. The most common adverse events in treated patients, reported in at least 4%, included pyrexia, exacerbation of AD, nasopharyngitis, headache, aphthous ulcer, chills, influenza, and fatigue. No treatment-related deaths were observed. 

IN PRACTICE:

“Results from IGNITE and HORIZON support the use of rocatinlimab monotherapy in adult patients with moderate-to-severe atopic dermatitis and the potential for additional benefit of rocatinlimab when combined with ad hoc topical therapy,” the authors wrote. “Safety was consistent with the previous phase 2b study, and rocatinlimab was generally well tolerated, with a low incidence of TEAEs [treatment-emergent adverse events] leading to treatment discontinuation,” they added.

SOURCE:

The study was led by Emma Guttman-Yassky, MD, Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York City, and was published online on November 25, 2025, in The Lancet.

LIMITATIONS:

The 24-week study duration might not have captured the full extent of the rocatinlimab treatment response. The IGNITE study was not designed to detect statistically significant differences between the 300-mg and 150-mg rocatinlimab doses. The inclusion of treatment-experienced patients with harder-to-treat AD might have influenced the magnitude of observed efficacy. 

DISCLOSURES:

The study was funded by Amgen and Kyowa Kirin. Guttman-Yassky and several other authors reported receiving research grants or having other ties for multiple pharmaceutical companies including Amgen and Kyowa Kirin. Two authors reported being employees of Kyowa Kirin and holding stocks in the company. Five authors declared being employees of Amgen.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.