Treg-Targeting Rezpegaldesleukin Demonstrates Dual Benefit for Asthma and Atopic Dermatitis

Nektar Therapeutics reported new phase 2b data showing that the investigational IL-2 pathway agonist rezpegaldesleukin improved asthma control in adults with moderate-to-severe atopic dermatitis (AD) who also had a history of asthma. Investigators presented the results from the REZOLVE-AD trial during a late-breaking oral session at the 2025 American College of Allergy, Asthma & Immunology (ACAAI) Annual Scientific Meeting.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,” lead author Jonathan Corren, MD, associate clinical professor of medicine and pediatrics at the David Geffen School of Medicine, University of California, Los Angeles, said in a statement. “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.”

REZOLVE-AD

The REZOLVE-AD study enrolled 393 participants with moderate-to-severe AD who had not previously received treatment with biologic or JAK inhibitor therapies. Of these, 99 reported a history of asthma and had Asthma Control Questionnaire–5 (ACQ-5) data at baseline and week 16. Investigators assessed 3 rezpegaldesleukin dose regimens. All 3 dose arms reduced mean observed ACQ-5 scores at week 16. Two doses, 24 μg/kg every 2 weeks and 24 μg/kg every 4 weeks, reached statistical significance versus placebo (P <.05 for both). Over the same interval, mean ACQ-5 scores in the placebo arm worsened, according to Nektar.

The gains were greater among participants with partly controlled or uncontrolled asthma, the company reported. Among the 53 participants whose baseline ACQ-5 scores measured 0.5 or less, at least half achieved clinically significant improvement (reducion of 0.5-point or more) at week 16 across all active treatment arms, compared with 13% in the placebo group. Placebo-adjusted reductions in this subgroup ranged from 0.7 to 1.0.

In the 25 participants with uncontrolled asthma at baseline (1.5 ACQ-5 or greater), all active doses produced meaningful reductions in mean ACQ-5 scores at week 16, with all dose arms meeting statistical significance (P <.05). Placebo-adjusted ACQ-5 reductions in this uncontrolled subgroup ranged from 1.0 to 1.4. In the study arm dosed with 24 μg/kg every 2 weeks, 75% of participants with uncontrolled dsease achieved a clinically significant ACQ-5 improvement.

Treg Mechanism May Span Inflammatory Diseases

“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,” Jonathan Zalevsky, PhD, chief research and development officer at Nektar, commented in the statement. “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.”

“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.”

All AD Endpoints Improved

Across the full trial population, the 24 μg/kg dose given every 2 weeks also improved all primary and secondary AD endpoints at week 16 compared with placebo. Reported improvements included mean percent change in Eczema Area and Severity Index (EASI) (P <.001), EASI-75 (P <.001), EASI-90 (P <.05), Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) 0/1 (P <.05), and ≥4-point Itch Numeric Rating Scale (NRS-Itch) response (P <.01). Notably, the effects were consistent across baseline disease severity, region, and presence of asthma, Nektar said.

Positve Cross-Over Efficacy

The results presented at ACAAI also included 24-week data gathered from 42 placebo-traeted participants who crossed over at week 16 to high-dose rezpegaldesleukin (24 μg/kg every 2 weeks). At week 24, the EASI-75 response rate reached 60%; vIGA-AD 0/1 reached 33%; EASI-90 reached 37%; and among participants with baseline NRS-Itch of 4 or greater, 50% achieved a clinically significant itch response. These findings support a 24-week induction period for phase 3 evaluation using the 24 μg/kg every-2-week regimen.

Nektar expects 52-week maintenance data from REZOLVE-AD in Q1 2026.

In February 2025, the FDA granted Fast Track designation for rezpegaldesleukin to treat moderate-to-severe atopic dermatitis in patients 12 years and older inadequately controlled with topical therapies or for whom they are unsuitable. In July 2025, the FDA also granted Fast Track designation for severe alopecia areata in patients 12 years and older weighing at least 40 kg. Nektar plans to report topline Phase 2b results in alopecia areata in December 2025.¹

References

New data from REZOLVE-AD study of rezpegaldesleukin presented in late-breaking oral abstract presentation at ACAAI 2025 annual scientific meeting. News release. Nektar Therapeutics. November 8, 2025. https://ir.nektar.com/node/22326/pdf

Harb H, Chatila TA. Regulatory T-cells in asthma. Curr Opin Allergy Clin Immunol. 2023;23(2):151–157. doi: 10.1097/ACI.0000000000000887