Rezpegaldesleukin Shows Promise for AD, Comorbid Asthma, With Jonathan Corren, MD

Rezpegaldesleukin, a first-in-class IL-2 receptor pathway agonist, significantly improved skin outcomes and asthma control in patients with moderate-to-severe atopic dermatitis (AD), according to late-breaking data from the Phase 2b REZOLVE-AD trial presented at the 2025 American College of Allergy, Asthma, & Immunology (ACAAI) Annual Scientific Meeting in Orlando, Florida.1

“This is a very new approach by trying to augment T regulatory activity, which has a potential for controlling inflammation in a lot of different ways, and trying to do it without any immunosuppression,” investigator Jonathan Corren, MD, associate clinical professor of medicine and pediatrics at the David Geffen School of Medicine, University of California, Los Angeles. “That's what really makes this a unique approach. What we saw in atopic dermatitis was extremely encouraging. [I am] looking forward to larger trials to hopefully confirm these same findings.”

Rezpegaldesleukin selectively expands regulatory T-cell activity, controlling inflammation without broad immunosuppression,” said Dr. Jonathan Corren, Associate Clinical Professor at UCLA. “In patients with both AD and asthma, we observed meaningful reductions in Asthma Control Questionnaire-5 scores, suggesting benefits beyond the skin.”

The REZOLVE-AD trial enrolled 393 adults, including 99 with a history of asthma. Participants received subcutaneous rezpegaldesleukin at 24 μg/kg every 2 weeks, 18 μg/kg every 2 weeks, 24 μg/kg every 4 weeks, or placebo over a 16-week induction period.

Patients in the 24 μg/kg every 2 weeks group achieved statistically significant improvements across all endpoints. At week 16, At week 16, rezpegaldesleukin produced significant improvements in Eczema Area and Severity Index (EASI; P <.001), EASI-75 (P <.001), EASI-90 (P <.05), validated Investigator Global Assessment (vIGA-AD; P <.05), and Numerical Rating Scale Itch (NRS-Itch; ≥4-point reduction, P <.01). Benefits were consistent regardless of baseline disease severity, sex, geographic region, or asthma comorbidity.1

Patients with partially controlled or uncontrolled asthma showed the most pronounced reductions in ACQ-5 scores. Among those with uncontrolled asthma at baseline, 75% achieved clinically meaningful improvement.

Crossover data from 42 placebo patients who switched to high-dose rezpegaldesleukin at week 16 confirmed sustained efficacy at week 24. At crossover, 60% of patients achieved EASI-75, 37% reached EASI-90, 33% achieved vIGA-AD 0/1, and 50% reported ≥4-point reductions in Itch NRS. These results support a 24-week induction period before transitioning to maintenance therapy.

Safety was favorable, with no serious immunosuppressive, systemic, or ocular adverse events reported. The US Food & Drug Administration granted Fast Track designation for rezpegaldesleukin in patients aged ≥ 12 years with moderate-to-severe AD not adequately controlled with topical therapies, announced by Nektar Therapeutics on February 10, 2025.2

“This research represents a very new way of looking at the modulation of allergic atopic diseases, from the perspective [of] you're not blocking a single mediator in the case of IL-5 or IL-13, IL-31, or IgE, but you're really trying to change the profile of regulatory cells that can dampen the entire inflammatory response all at once,” Corren said. “This gives us high hopes that, ultimately, maybe there will be better effects, longer-lived effects, which will be unique and differentiated from what we currently have available to us.”

References

1. Derman C. Rezpegaldesleukin Shows Strong Phase 2b Results for Atopic Dermatitis, Asthma. HCPLive. Published November 21, 2025. Accessed December 12, 2025. https://www.hcplive.com/view/rezpegaldesleukin-shows-strong-phase-2b-results-atopic-dermatitis-asthma

2. Nektar Therapeutics Receives Fast Track Designation for Rezpegaldesleukin for the Treatment of Moderate-to-Severe Atopic Dermatitis. Nektar Therapeutics. Published February 10, 2025. Accessed December 12, 2025. https://ir.nektar.com/news-releases/news-release-details/nektar-therapeutics-receives-fast-track-designation.