OX40 Inhibitor Rocatinlimab Shows Significant Response in Combination with Topical Therapy for AD

In the phase 3 ROCKET-SHUTTLE clinical trial, the OX40 receptor–targeting antibody rocatinlimab, given every 4 weeks with background topical corticosteroids (TCS) and/or calcineurin inhibitors (TCIs), achieved significant improvements in signs and symptoms of moderate-to-severe atopic dermatitis compared with placebo, according to findings presented Thursday in a late-breaking abstract session at the European Academy of Dermatology and Venerology 2025 Annual Meeting in Paris, September 17-20, 2025.

Eric Simpson, MD, MCR
Courtesy of Oregon Health & Science University

At week 24, presenting author Eric Simpson, MD, professor of Dermatology, Oregon Health & Science University, Portland, Oregon, and colleagues observed Eczema Area and Severity Index (EASI)-75 responses in 52.3% of study participants receiving rocatinlimab 300 mg and 54.1% of those on 150 mg, vs approximately half that number (23.5%) among placebo-treated participants (P <.001 for both). Similarly, 26.1% and 25.8% of participants in the respective active treatment arms achieved validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA-AD) of 0 (clear) or 1 (almost clear), with a 2-point or greater reduction from baseline, compared with 12.2% of placebo-treated participants (P <.001 for both).

ROCKET-SHUTTLE enrolled 746 adults with inadequate response to prior medium-to-high potency topical corticosteroids or topical calcineurin inhibitors, nearly 60% of whom had previously received systemic therapy and one quarter prior biologics or JAK inhibitors.

Simpson et al randomly assigned participants to rocatinlimab 300 mg, rocatinlimab 150 mg, or placebo in a 5:4:4 ratio. In all cases, background low-to-medium potency topical agents were tapered according to clinical response.

The late-stage trial also met key secondary endpoints, including EASI-90 and earlier achievement of EASI-75 and vIGA-AD 0/1 at week 16. Investigators observed progressive improvement without evidence of plateau at week 24, suggesting the potential for continued benefit beyond the treatment window studied, according to the study abstract.

Safety Findings

Simpson and the research team reported adverse events (AEs) at similar rates across arms (71.5% in both rocatinlimab groups vs 67.2% in the placebo group). Results showed that infections also occurred in approximately similar proportions of each group: 35.4% of the 300-mg group, 39.9% of the 150-mg group, and 38.0% of the placebo group. The authors also observed serious adverse events more frequently with rocatinlimab (3.1% at 300 mg; 4.4% at 150 mg) than with placebo (0.9%). However, no specific event category was reported in more than 1 participant. Discontinuations due to severe AEs was reportedly infrequent (1.8% or less across groups).

These findings add to earlier monotherapy results from the ROCKET-HORIZON and IGNITE trials, supporting the therapeutic potential of OX40 receptor blockade in AD.

The Promise of Inhibiting OX40 Signaling

The pathogenesis of atopic dermatitis is closely tied to T-cell–driven immune dysregulation, with OX40 signaling on activated T cells serving as a central amplifier of chronic inflammation and disease flares. Rocatinlimab (Amgen, Kyowa Kirin) is a first-in-class, humanized monoclonal antibody that targets the OX40 receptor to reduce pathogenic T-cell activity and restore immune balance. It is by interrupting this co-stimulatory pathway that the therapy both reduces inflammation and, importantly, also to influence the long-term course of disease.

"In a diverse, treatment-experienced AD patient population failing prior topicals, [rocatinlimab] with concomitant TCS (low-to-medium potency)/TCI demonstrated statistically significant and clinically meaningful improvements vs [placebo] in AD clinical signs and symptoms with progressive efficacy and no plateau at week 24," Simpson et al concluded in the study abstract.

Rocatinlimab’s ability to enhance disease control when combined with standard topical treatments underscores its potential role as a T-cell–rebalancing therapy in a treatment landscape increasingly guided by immunologic endotypes.

References

1. Simpson E. Rocatinlimab with concomitant topical therapy significantly improved clinical signs and symptoms of atopic dermatitis in adults: Results from the phase 3 ROCKET-SHUTTLE trial. Presented at: 2025 European Academy of Dermatology and Venerology Congress; September 17-20; Paris, France.

2. Abdelhalim A, Yilmaz O, Berair ME, Torres T. A narrative review of the OX40-OX40L pathway as a potential therapeutic target in atopic dermatitis: Focus on rocatinlimab and amlitelimab. Dermatol Ther (Heidelb). 2024;12:3197-3210. doi:10.1007/s13555-024-01308-8