PARIS — The anti-OX40 monoclonal antibody rocatinlimab produced clinically meaningful improvements in adults with moderate-to-severe atopic dermatitis both as monotherapy and when used with topical agents, according to phase 3 ROCKET trial data presented recently at the European Academy of Dermatology and Venereology (EADV) 2025 Congress.

Describing the significance of the findings, Emma Guttman-Yassky, MD, of Icahn School of Medicine at Mount Sinai, New York, said, “While it is a very exciting time in atopic dermatitis and we already have some new drugs to treat our patients, we still have an unmet need.” 

“Many of our patients still do not achieve full disease control or have some tolerability or safety issues on current treatments, regardless of whether it’s the old treatments or the new treatments. Our patients want fewer administration of drugs, and they want something that may modify their disease,” she added.

That goal has turned attention to agents that target the OX40 — either the receptor (OX40) or its ligand (OX40L) — to dampen pathogenic T cells that release proinflammatory cytokines and sustain T-cell memory responses in atopic dermatitis.

Guttman-Yassky told Medscape Medical News, “This drug holds the promise for disease modification. This is a different type of treatment. It’s a little bit slower [than other approaches], but once it kicks in, it has continuous improvement.”

The ROCKET Trials

In both the ROCKET-IGNITE monotherapy and ROCKET-SHUTTLE combination-therapy trials, significantly greater proportions of patients treated with rocatinlimab (150 mg or 300 mg subcutaneously every 4 weeks) than with placebo met both co-primary endpoints at 24 weeks.

The endpoints were achievement of at least a 75% reduction from baseline in Eczema Area and Severity Index (EASI-75) and a validated Investigator Global Assessment (vIGA) score of 0 or 1 with at least a 2-point improvement from baseline.

In the monotherapy trial, EASI-75 was achieved by 42.3% of patients receiving rocatinlimab 300 mg (n = 326) and 36.3% receiving 150 mg (n = 215) vs 12.8% with placebo (n = 219).

In the combination trial, EASI-75 rates were 52.3% and 54.1% with rocatinlimab 300 mg (n = 287) and 150 mg (n = 229), respectively, vs 23.5% with placebo (n = 230).

vIGA 0/1 at week 24 was reached by 23.6% and 19.1% in the 300-mg and 150-mg groups, respectively, vs 8.7% with placebo in the monotherapy trial. Corresponding rates in the combination trial were 26.1% and 25.8% with rocatinlimab vs 12.2% with placebo.

Longer-term, Guttman-Yassky expects higher proportions of patients to achieve EASI-75 and potentially EASI-90 and EASI-100. “I expect that maybe some populations of patients that didn’t respond to other treatments will respond here,” she said.

ROCKET Program: Combination Results and Next Steps

IGNITE and SHUTTLE are part of a broader phase 3 program of eight trials evaluating the efficacy and safety of rocatinlimab in moderate-to-severe atopic dermatitis. Both of these 24-week studies enrolled adults only, but additional trials are assessing longer-term treatment and adolescent populations.

Eric Simpson, MD, Oregon Health & Science University, Portland, who presented the combination study results, said the data show a steady, progressive accumulation of responders over time toward the EASI-75 endpoint. He noted minimal differences between the two dosing groups and a clear separation from placebo emerging early, particularly by week 8.

Participants receiving combination therapy — which allowed concomitant low-to-medium potency topical corticosteroids with or without topical calcineurin inhibitors — were also more likely than those receiving placebo to report improvements in itch (40.7%-44.5% vs 23.7%) and skin-related pain (45.7%-47.2% vs 27.1%).

“We’re very curious to see these kinds of rebalancing treatments — how they’re going to do over the long haul. Are these numbers going to continue to increase over time?” Simpson said.

Regarding safety, both Simpson and Guttman-Yassky reported no new safety signals. Most adverse events were mild to moderate, with no meaningful differences in serious events vs placebo and no fatal events. The most common adverse events with rocatinlimab were fever, chills, and headache, typically occurring early in treatment and usually resolving within 48 hours.

Paradigm Shift in Treatment

Commenting for Medscape Medical News, Thomas Bieber, MD, of the Christine Kühne – Center for Allergy Research and Education (CK-CARE), Davos, Switzerland, and Bieber Dermatology Consulting, Bonn, Germany, said that OX40-targeting agents such as rocatinlimab and the OX40L-targeting amlitelimab act “on the immune cascade at a level that allows a deeper and larger impact on the T-cell response. And this impact can be so substantial that we think that at least a good part of the so-called tissue memory for inflammation can be dramatically reduced.”

This bodes well for durable control, he suggested, but longer-term data are needed to confirm whether these agents truly modify disease. Key questions include treatment duration and whether therapy could eventually be paused or stopped, or spaced out more than is currently possible.

“The biggest mistake is to try to compare the short-term data for OX40-targeting therapies with other drugs,” such as 16-week data from classically available drugs such as dupilumab [Dupixent] or lebrikizumab [Ebglyss], Bieber cautioned. “This makes no sense, because we know that the mode of action of these new drugs is slower than that of the available drugs. It would be unfair to compare these very early endpoints,” he added.

“It’s a paradigm shift in drug development and, ultimately, in the management of the patients. If everything goes well, as we expect and hope, I think that these new drugs will be available by the end of 2027,” Bieber said.

The ROCKET studies were funded by Amgen Inc. and Kyowa Kirin Co., Ltd. 

Guttman-Yassky and Simpson reported receiving research grants (paid to their institutions) and honoraria or consultation fees from Amgen Inc., as well as multiple other pharmaceutical companies involved in the development or manufacture of dermatologic products. Bieber has been a speaker, consultant, and/or investigator for various biotechnology and pharmaceutical companies, not including Amgen. He is the founder and chairman of the board of the non-profit biotech Davos Biosciences AG within the international Kühne-Foundation and founder of the consulting firm Bieber Dermatology Consulting. 

Sara Freeman is a freelance medical journalist based in London, England.