Rezpegaldesleukin Potentially Promising for Atopic Dermatitis

An earlier version of this article was published by Dermatology Times^®.

After treating patients for 16 weeks with the investigational biologic therapy rezpegaldesleukin (Nektar Therapeutics) for atopic dermatitis (AD), the global phase 2b REZOLVE-AD study (NCT06136741) has met its primary and key secondary end points.¹ This study has enrolled 393 patients with moderate to severe disease.

Rezpegaldesleukin targets the interleukin-2 receptor complex to stimulate the proliferation of regulatory T cells (Tregs). It was granted fast track designation by the 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, Nektar Therapeutics, in a statement.¹ "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."

The trial began in November 2023 and is currently taking place at 110 sites around the world.³ 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) score of 3. Patients were randomized to receive 1 of 3 doses of rezpegaldesleukin subcutaneously: 24 µg/kg every 2 weeks (high dose), 18 µg/kg every 2 weeks (middle dose), or 24 µg/kg every 4 weeks (low dose), or placebo every 2 weeks.

Following 16 weeks of rezpegaldesleukin treatment in the REZOLVE-AD study, primary and key secondary end points have been met. | Image Credit: © slobodyan_78-stock.adobe.com

All 3 dose arms saw statistically significant and rapid improvements in EASI compared with placebo (P < .001), meeting the primary end point. Secondary endpoints of EASI-75 (patients who achieve ≥ 75% reduction in EASI from baseline), EASI-50 (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 at least a 2-point reduction from baseline. The investigators also observed a significant reduction of at least 4 points on the Itch Numerical Rating Score. At week 16, approximately 25% of patients in the high-dosage group reached EASI-90 reduction 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," said Jonathan Silverberg, MD, PhD, MPH, professor of dermatology, George Washington University School of Medicine and Health Sciences, in a statement.¹ "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."

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

The results of the REZOLVE-AD study will be presented at an upcoming conference. Long-term maintenance data are expected in early 2026. Rzpegaldesleukin is also being evaluated in the REZOLVE-AA study (NCT06340360), a randomized, double-blind, placebo-controlled phase 2b clinical trial for the treatment of patients with severe to very severe alopecia areata.⁴

"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, Department of Dermatology, and associate professor of dermatology, Indiana University School of Medicine, in a statement. "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 stopic 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. Bader K. Rezpegaldesleukin receives fast track designation for moderate to severe AD. Dermatology Times. February 10, 2025. Accessed July 1, 2025. https://www.dermatologytimes.com/view/rezpegaldesleukin-receives-fast-track-designation-for-moderate-to-severe-ad

3. A phase 2b study to evaluate rezpegaldesleukin (rezpeg) in the treatment of adult patients with moderate-to-severe atopic dermatitis (REZOLVE-AD). ClinicalTrials.gov. Updated June 26, 2025. Accessed July 1, 2025. https://clinicaltrials.gov/study/NCT06136741

4. A phase 2b study to evaluate rezpegaldesleukin (rezpeg) in the treatment of severe to very severe alopecia areata in adult patients (Rezolve AA). ClinicalTrials.gov. Updated April 2, 2025. Accessed July 1, 2025. https://clinicaltrials.gov/study/NCT06340360