REZOLVE-AD Trial Results Show Promise for Rezpegaldesleukin in Atopic Dermatitis

Image Credit: © dermnetnz.org

Nektar Therapeutics has shared positive data from the ongoing phase 2b REZOLVE-AD study of investigational rezpegaldesleukin for the treatment of atopic dermatitis (AD).¹ The global study, which includes 393 patients with moderate to severe disease, has met primary and key secondary endpoints after 16 weeks of treatment. Rezpegaldesleukin is an investigational biologic therapy that targets the IL-2 receptor complex to stimulate the proliferation of regulatory T cells. It was granted fast track designation by the US Food and Drug Administration (FDA) in February of this year.²

"We believe that the REZOLVE-AD study results clearly demonstrate that Nektar has established a new biology and harnessed the promise of Tregs as an important potential therapeutic modality to treat inflammatory skin disorders and other autoimmune conditions," said Howard W. Robin, President and CEO of Nektar Therapeutics. "These compelling efficacy findings are further boosted by the translational data that show, for the first time, that rezpegaldesleukin also reduced key markers of Th2 inflammation in atopic dermatitis. With this validation in atopic dermatitis, we also look forward to reporting results in the fourth quarter of this year for rezpegaldesleukin in alopecia areata."¹

The trial began in October 2023 and is currently taking place at 110 sites around the world. Eligible participants began the study with a minimum Eczema Area and Severity Score (EASI) score of 16.0, a minimum Body Surface Area (BSA) of 10% and a minimum validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) of 3. Patients were randomized to receive 3 doses of rezpegaldesleukin subcutaneously. These dosages included a high dose of 24 µg/kg every 2 weeks, a middle dose of 18 µg/kg every 2 weeks, and a low dose of 24 µg/kg every 4 weeks, or placebo every 2 weeks.

All 3 dose arms saw statistically significant and rapid improvements in EASI compared to placebo (p < 0.001), meeting the primary endpoint. Secondary endpoints of EASI-75 (percent of patients who achieve ≥75% reduction in EASI from baseline), EASI-50 (percent of patients who achieve ≥50% reduction in EASI from baseline), and average BSA improvement, were also met. A large percentage of patients taking the high or middle dose of rezpegaldesleukin achieved a score of 0 or 1 on the vIGA-AD with a ≥ 2-point reduction from baseline. They also observed a significant ≥ 4-point reduction in the Itch Numerical Rating Score (Itch NRS). At week 16, approximately 25% of patients in the high dosage group reached a ≥ 90% reduction in EASI from baseline after 16 weeks.

"These data from REZOLVE-AD show a fast onset of both EASI response and itch relief within the first few doses of rezpegaldesleukin treatment, which are important metrics for physicians as they assess treatment options in atopic dermatitis," Jonathan Silverberg, MD, PhD, MPH, Professor of Dermatology at George Washington University School of Medicine and Health Sciences, said in a statement. "This shows the advantage of a broad-based Treg mechanism over other immune-modulation approaches in development to treat the disease. Additionally, we don't see any increased risk of incidence of conjunctivitis, oral herpes, or oral ulcers with this mechanism of action as we do with other mechanisms."¹

The safety profile of rezpegaldesleukin in the REZOLVE-AD aligns with what has been established in previous research. The most frequent adverse events were local injection site reactions, which were mild or moderate. Other commonly observed adverse effects were eosinophilia, pyrexia, headaches, and arthralgia. No increased risk of conjunctivitis, oral ulcers, or infections, including oral herpes, was observed in participants treated with rezpegaldesleukin.

The results of the REZOLVE-AD study will be presented at an upcoming conference later this year. Long-term maintenance data is expected in early 2026. Rzpegaldesleukin is also being evaluated in the REZOLVE-AA study, a randomized, double-blind, placebo-controlled phase 2b clinical trial for the treatment of patients with severe to very severe alopecia areata.

"These REZOLVE-AD results present a new therapeutic hypothesis for treatment of dermatological diseases and the investigators are looking forward to rezpegaldesleukin advancing in development in atopic dermatitis," said David Rosmarin, MD, Chair of the Department of Dermatology and Associate Professor of Dermatology at the Indiana University School of Medicine. "With the establishment of this efficacy profile in the dermatological setting of atopic dermatitis, we are also eager to see the upcoming results from the ongoing REZOLVE-AA study in patients with severe to very-severe alopecia areata."¹

References

1. REZOLVE-AD Phase 2b Study of Rezpegaldesleukin Meets Primary and Key Secondary Endpoints in Patients with Moderate-to-Severe Atopic Dermatitis. News release. Nektar Therapeutics. June 24, 2025. Accessed June 27, 2025. https://ir.nektar.com/news-releases/news-release-details/rezolve-ad-phase-2b-study-rezpegaldesleukin-meets-primary-and

2. Nektar Therapeutics receives fast track designation for rezpegaldesleukin for the treatment of moderate-to-severe atopic dermatitis. News release. PRNewswire. February 10, 2025. Accessed June 27, 2025. https://www.prnewswire.com/news-releases/nektar-therapeutics-receives-fast-track-designation-for-rezpegaldesleukin-for-the-treatment-of-moderate-to-severe-atopic-dermatitis-302371995.html