Rezpegaldesleukin Shows Strong Phase 2B Results for Atopic Dermatitis, Asthma

A phase 2B trial supports rezpegaldesleukin, an IL-2 receptor pathway agonist, for the treatment of atopic dermatitis (AD) and asthma. James Treat, MD, from Children’s Hospital of Philadelphia, presented the 16-week induction therapy findings from the REZOLVE-AD as a late breaker at the 2025 American College of Allergy, Asthma, & Immunology (ACAAI) Annual Scientific Meeting in Orlando, Florida, on Saturday, November 8.1

“Given that approximately one in four patients with atopic dermatitis also have asthma, improving asthma symptoms is a significant consideration in clinical treatment decisions," said lead author Jonathan Corren, MD, an associate clinical professor of medicine and pediatrics at the David Geffen School of Medicine at the University of California, in a statement.2 "The results with rezpegaldesleukin in patients with atopic dermatitis and comorbid asthma demonstrate that promotion of Treg activity may also have benefits to the lower airways, an observation which warrants further investigation."

Rezpegaldesleukin offers a novel therapeutic approach for treating AD and asthma, selectively expanding the function of regulatory T-cells. The US Food & Drug Administration (FDA) granted Nektar Therapeutics the Fast Track Designation for rezpegaldesleukin to treat moderate-to-severe atopic dermatitis in adults and children ≥ 12 years who are not adequately controlled with topical prescription therapies.2

REZOLVE-AD, a randomized, double-blind, placebo-controlled, multicenter phase 2b trial, evaluated rezpegaldesleukin in 393 adults with moderate-to-severe AD.1 Participants were randomized 3:3:3:2 to receive subcutaneous rezpegaldesleukin 24 μg/kg every 2 weeks (n = 104), 18 μg/kg every 2 weeks (n = 106), 24 μg/kg every 4 weeks (n = 110), or placebo (n = 73).

The study assessed AD severity using the Eczema Area and Severity Index (EASI), validated Investigator Global Assessment (vIGA-AD), and Numerical Rating Scale Itch (NRS-Itch). Investigators also collected the Asthma Control Questionnaire-5 (ACQ-5) at baseline and week 16 from patients with asthma (n = 99), including 25 with uncontrolled asthma (baseline ACQ-5 ≥1.5).

Rezpegaldesleukin 24 μg/kg every 2 weeks brought significant improvements in mean percent change in EASI (P <.001), EASI-75 (P <.001), EASI-90 (P <.05), vIGA-AD 0/1 (P <.05), NRS-Itch response (≥4-point reduction) (P <0.01) at Week 16, compared with placebo. Corren and colleagues observed improvements across baseline characteristics, including disease severity, sex, region, and asthma comorbidity.1

Among patients with a history of asthma, patients experienced a reduction in ACQ-5 scores with all 3 rezpegaldesleukin doses at week 16, though only the 24 μg/kg every 2 or 4 weeks achieved statistical significance compared to placebo (P <.05). The study showed more pronounced improvements in patients with only partially controlled or uncontrolled asthma.1

In total, 75% of patients with uncontrolled asthma at baseline experienced clinically significant improvement with rezpegaldesleukin. Among patients with a baseline ACQ-5 of ≥ 0.5 (n = 53), at least half of them experienced clinically significant improvement, indicated by a ≥ 0.5-point reduction in ACQ-5 at week 16.1

At ACAAI, Treat also presented crossover data, including 42 placebo patients who crossed over at week 16 and continued in the study on a treatment escape arm to receive high-dose rezpegaldesleukin 24 µg/kg every 2 weeks. At crossover week 24, 60% had an EASI-75 response, 33% had vIGA-AD 0/1 response, 37% had an EASI-90 response, and 50% had an Itch NRS response.1

This data supports rezpegaldesleukin 24 μg/kg every 2 weeks with a 24-week treatment induction period. The trial observed no new safety signals.

“These observations of improvement in asthma control in REZOLVE-AD support the broad potential of rezpegaldesleukin's Treg mechanism across multiple T-cell mediated inflammatory diseases," said Jonathan Zalevsky, PhD, chief research and development officer of Nektar, in a statement.2 "The data demonstrate that rezpegaldesleukin could offer a unique and differentiated innovative treatment for atopic dermatitis, particularly as these findings have not been observed with other biologic mechanisms recently approved or in advanced development.”

References

1. Corren J, Lio P, Silverberg J, et al. REZPEGALDESLEUKIN, NOVEL TREG-INDUCING THERAPY, DEMONSTRATES EFFICACY IN ATOPIC DERMATITIS AND ASTHMA IN PHASE 2B TRIAL. Annals of Allergy, Asthma & Immunology. 2025;135(5):S4. doi:https://doi.org/10.1016/j.anai.2025.10.021

2. New Data from REZOLVE-AD Study of Rezpegaldesleukin Presented in Late-Breaking Oral Abstract Presentation at ACAAI 2025 Annual Scientific Meeting. Nektar Therapeutics. November 8, 2025. https://ir.nektar.com/news-releases/news-release-details/new-data-rezolve-ad-study-rezpegaldesleukin-presented-late. Accessed November 21, 2025.